Background: The concept of clinical control has been proposed as an instrument for evaluating patients with COPD. However, the possible association between clinical control, reduced symptom severity and HRQoL has yet to be confirmed., Methods: This multicentre, prospective and observational study was carried out in 15 pulmonology clinics in Spain. The patients were followed up for six months, with a baseline visit (V0), followed by visits at three months (V1) and six months (V2). Clinical control was determined at V1, with the application of both clinical criteria and the COPD assessment test (CAT). All patients reported their symptoms by a validated symptom diary (E-RS) using a portable device, and their HRQoL was assessed using the EQ5D questionnaire. The relationship between clinical control and E-RS and HRQoL during follow-up was assessed with t -test., Results: A total of 126 patients were screened. After application of the inclusion/exclusion criteria, 93 were finally included (mean age 66 ± 8 years, 84.9% male), with a mean FEV 1 predicted of 49.8% ± 16.5%. Of these patients, 44 (47.3%) achieved clinical control at V1, according to CAT criteria, and 50 (53.8%), according to clinical criteria. The E-RS scores differed between controlled and uncontrolled patients at all time points, both according to CAT (mean differences of -4.6, -5.6 and -6.2 units at V0, V1 and V2, respectively, p<0.005 for all comparisons) and to clinical criteria (mean differences of -3.3, -5-6 and -4.99 units, respectively, p<0.005 for all comparisons). The controlled patients also presented a significantly better HRQoL, measured by the EQ5D questionnaire (mean difference 0.13 and 0.10 at V2 by CAT or clinical criteria, respectively, p<0.05)., Conclusion: Clinical control in patients with COPD, whether measured by CAT or by clinical criteria, is associated with a lower symptom load and a better HRQoL., Competing Interests: Dr. Alcázar-Navarrete reports grants, non-financial support and personal fees from GSK, grants, personal fees and non-financial support from Novartis AG, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial support from Chiesi, grants, personal fees and non-financial support from Laboratorios Menarini, personal fees from Gebro, personal fees and non-financial support from Astra-Zeneca, personal fees from Laboratorios Rovi, personal fees from Laboratorios Ferrer, grants, personal fees, non-financial support from Menarini, outside the submitted work. Dra. Fuster has nothing to disclose. Dra García-Sidro reports personal fees from GSK, Pfizer, Novartis AG, Menarini, Boehringer Ingelheim, Astra-Zeneca, Gebro and Laboratorios Rovi, outside the submitted work. Dr. García Rivero has nothing to disclose. Dr. Abascal-Bolado has nothing to disclose. Dr. Pallarés-Sanmartín has received lecture fees, consultancy fees and/or support for conference attendance from various pharmaceutical companies such as Novartis, GlaxoSmithKline, Chiesi, Boehringer Ingelheim, Mundipharma, Menarini, Laboratorios Esteve, Astra Zeneca, Teva Pharmaceutical, Ferrer, Rovi, Bial, Faes Farma, ALK Abelló and Gebro Pharma outside the submitted work. Dr. Marquez- Martín has nothing to disclose. Dr. Valido Morales has received lecture fees, consultancy fees and/or support for conference attendance from various pharmaceutical companies, such as GlaxoSmithKline, Chiesi, Boehringer Ingelheim, Menarini, Pfizer, Novartis, Laboratorios Esteve, Teva Pharmaceutical, Ferrer, Rovi, Astra Zeneca, Bial, Grifols, Faes Farma and Gebro Pharma, outside the submitted work. Dr. Callejas González has received lecture fees, consultancy fees and/or support for conference attendance from various pharmaceutical companies, such as GlaxoSmithKline, Chiesi, Boehringer Ingelheim, Mundipharma, Menarini, Pfizer, Novartis, Laboratorios Esteve, Teva Pharmaceutical, Ferrer, Rovi, Roche, Astra Zeneca, Bial, Actelion, Grifols, CSL Behring, Faes Farma and Gebro Pharma, and reports personal fees from GlaxoSmithKline, personal fees from Chiesi, personal fees from Boehringer Ingelheim, personal fees from Mundipharma, personal fees from Menarini, personal fees from Pfizer, personal fees from Novartis, personal fees from Laboratorios Esteve, personal fees from Teva Pharmaceutical, personal fees from Ferrer, personal fees from Rovi, personal fees from Roche, personal fees from Astra Zeneca, personal fees from Bial, personal fees from Actelion, personal fees from Grifols, personal fees from CSL Behring, personal fees from Faes Farma, personal fees from Gebro Pharma, outside the submitted work. Dra. Palop reports personal fees from Astra Zeneca, GlaxoSmithKline, Chiesi, Boehringer -Ingelheim, Novartis, Teva, Menarini, Rovi, outside the submitted work. Dr. JA Riesco reports grants and personal fees from GSK, grants, personal fees and non-financial support from Pfizer, Novartis AG, Menarini, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial from Astra-Zeneca, Grants and personal fees from Gebro, personal fees from Laboratorios Rovi, outside the submitted work. Dr. Golpe reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Menarini, Rovi, Zambon, Grifols, Novartis, Ferrer, Gebro Pharma, Laboratorios Esteve and GlaxoSmithKline, outside the submitted work. Dr. Soler-Cataluña reports speaking fees from Laboratorio Esteve, Mundipharma, grants, personal fees, speaking fees from AstraZeneca, grants, personal fees, non-financial support from Boehringer Ingelheim, personal fees from Bial, personal fees from Ferrer, personal fees, non-financial support from Menarini, personal fees, non-financial support from Novartis, personal fees from Rovi and Teva; consulting fees from AirLiquide, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Laboratorios Esteve, Mundipharma grants, personal fees from Chiesi, personal fees from Ferrer, grants, personal fees from; research grants from GlaxoSmithKline and Boehringer Ingelheim, outside the submitted work. Marc Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Novartis, Sanofi and Grifols and research grants from GlaxoSmithKline and Grifols; reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Novartis, Sanofi and Grifols, grants from GlaxoSmithKline and Grifols., outside the submitted work. The authors report no other potential conflicts of interest for this work., (© 2020 Alcazar-Navarrete et al.)