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Depression is one of the most common mental disorders and will become one of the leading causes of disability in the world. Internet-based CBT programs for depression have been classified as well established following the American Psychological Association criteria for empirically supported treatments. The aim of this study is to analyze the cost effectiveness at 12-month follow-up of the Internet-based CBT program Smiling is fun with (LITG) and without psychotherapist support (TSG) compared to usual care. The perspective used in our analysis is societal. A sample of 296 depressed patients (mean age of 43.04 years; 76% female; BDI-II mean score = 22.37) from primary care services in four Spanish regions were randomized in the RCT. The complete case and intention-to-treat (ITT) perspectives were used for the analyses. The results demonstrated that both Internet-based CBT interventions exhibited cost utility and cost effectiveness compared with a control group. The complete case analyses revealed an incremental cost- effectiveness ratio (ICER) of (sic)-169.50 and an incremental cost-utility ratio (ICUR) of (sic)-11389.66 for the TSG group and an ICER of (sic)-104.63 and an ICUR of (sic)-6380.86 for the LITG group. The ITT analyses found an ICER of (sic)-98.37 and an ICUR of (sic)- 5160.40 for the TSG group and an ICER of (sic)-9.91 and an ICUR of (sic)496.72 for the LITG group. In summary, the results of this study indicate that the two Internet-based CBT interventions are appropriate from both economic and clinical perspectives for depressed patients in the Spanish primary care system. These interventions not only help patients to improve clinically but also generate societal savings., This study was financed by the Institute de Salud Carlos III of the Spanish Ministry of Economy and Competitiveness with the PI10/01083 grant (Eficacia y coste-efectividad de un programa de psicoterapia asistida por ordenador para el tratamiento de la depresion mayor en atencion primaria: estudio controlado, randomizado y cualitativo). The project also received funding from the Network for Prevention and Health Promotion in primary Care (RD12/0005) and GIBER Physiopathology Obesity and Nutrition (CB06/03) grants from the Institute de Salud Carlos III of the Ministry of Economy and Competitiveness (Spain). Both grants are co funded by European Regional Development Fund/European Social Fund) Investing in your future). The first author (PRS) has a Rio Hortega contract awarded by the Institute de Salud Carlos III (CM13/00115). The fourth author (JVL) has a Miguel Servet contract awarded by the Institute de Salud Carlos III (CP14/00087). http://www.isciii.esi. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.