Background: Maintenance antidepressant (AD) medication is the most commonly used preventive strategy in a highly recurrent disease, i.e. depression. Little is known about the discontinuation of maintenance AD use and the association with recurrence in daily clinical practice. The purpose was to examine the discontinuation rate of maintenance AD in daily clinical practice in recurrently depressed patients and the associated risk of recurrence. Methods: Prospectively AD maintenance medication and recurrence were examined in 172 euthymic patients with recurrent depression. AD user profiles before recurrence (nonusers, intermittent users, continuous users) were examined and related to recurrence over a 2-year follow-up period. Results: Less than half of the patients (42%) used AD continuously. Taking into account the minimal required adequate used dosage (≧20 mg fluoxetine equivalent), only 26% of the patients used AD as recommended by international guidelines. Despite continuous use of AD, 60.4% relapsed in 2 years. This relapse rate was comparable to the rate of the intermittent users (63.6%). In patients who stopped taking AD after remission and who received additional preventive CT, the recurrence rates were significantly lower than in non-AD-using patients treated with usual care (8 vs. 46%). Conclusions: The majority of recurrently depressed patients treated with AD discontinue maintenance AD therapy in daily primary and secondary clinical practice. AD seems to offer poor protection against relapse in this patient group. Patients who stopped using AD experienced less relapse, especially if they were treated with preventive CT. Alternative maintenance treatments (including preventive cognitive therapy after discontinuation of AD) should be studied in recurrently depressed patients with intermittent good remission, not only in secondary but also in primary care.