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Background: To assess gender differences in Quality of life (QoL) and in sociodemographic, clinical and psychological factors associated with impaired QoL in adults with long-standing type 1 diabetes mellitus (DM1)., Methods: Cross-sectional evaluation in a random cohort of DM1 adult patients from a tertiary care hospital. QoL was evaluated using translated and validated self-administered Diabetes QoL questionnaire (Es-DQoL), and results transformed into a 0-100 scale. Psychological assessment included a planned psychological interview and self-reported questionnaires (Beck Depression Inventory II, State-Trait Anxiety Inventory Form Y, Fear of hypoglycaemia Scale, Medical Outcomes Study Social Support Survey)., Results: A total of 312 patients (51.6% male; 38.2 ± 12.7 years; HbA 1c 7.5 ± 1.1% (58.5 ± 14.2 mmol/mol); 20.4 ± 12.0 years of DM1) were included in the analysis. Male and female subgroups showed similar sociodemographic and diabetes-related features and comparable social support. Among female patients, higher frequency of depression [31.7% (IC95% 26.2-40.8) vs. 14.9% (IC95% 10.1-20.8), p < 0.05] and anxiety [23.2% (IC95% 19.3-33.14) vs. 13.0% (IC95% 8.1-18.4), p < 0.05] and severity of depressive and anxious symptoms were also found. Compared to male patients, female patients showed lower QoL [75 (IC95% 73.6-77.5) vs. 80 (IC95% 75.7-83.1), p < 0.05] and scored significantly worse in subscale Diabetes-related worries [69 (IC95% 50.0-81.0) vs. 75 (IC95% 72.9-79.0), p < 0.05]. Fear of hypoglycemia and severity of depressive and anxious symptoms were factors independently associated to lower QoL in men and women while high frequency of glycemic excursions was a female-specific predictive one., Conclusions: Adult women with long-standing DM1 showed lower QoL probably related to higher frequency and severity of psychopathological syndromes. Depressive and anxious symptoms and, among women, exposure to glycemic excursions were identified as modifiable, QoL-related variables. Educational, technological and psychological interventions are needed in order to improve QoL in DM1 patients., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2020.)