Non-adherence to antidepressant drug treatment is common. In a recent study in depressed primary care patients, we reported a strong relationship between adherence and response after 6 months. With the use of a naturalistic design, the patients in that study were prospectively followed for 2 years. The purpose of the present study was to investigate the patients' long-term outcome and, in particular, to examine the impact of patients' treatment adherence on response, remission and relapse. Of the 1031 patients in the intent-to-treat (ITT) sample, 835 completed the study. After 2 years, the overall remission rate defined as a Montgomery–Åsberg Depression Rating Scale score of nine or less was 68% in the ITT sample analysed with the last observation carried forward (LOCF) technique, and 75% in observed cases. In total, 34% of the responders experienced at least one relapse. Response rates (LOCF) were significantly higher in adherent compared to non-adherent patients at week 24 [95% confidence interval (CI)=21.4–32.1], year 1 (95% CI=12.3–22.2) and year 2 (95% CI=9.2–19.0). Remission rates (LOCF) were also significantly higher in the group of adherent patients at week 24 (95% CI=9.6–21.5), year 1 (95% CI=10.0–21.5) and year 2 (95% CI=11.0–22.0). No relationship between adherence and relapse rate was observed, although the mean time from response to first sign of relapse was significantly longer in the adherent patients (95% CI=9–97 days). In conclusion, this 2-year follow-up study showed superior long-term recovery in patients who were adherent to antidepressant medication compared to non-adherent patients.