OBJECTIVE:To investigate whether Internet-based cognitive behaviour therapy (CBT) can prevent relapse in persons with partially remitted major depression after previous treatment. METHOD: Seventy-one women and 13 men (N = 84) with partially remitted major depression after treatment were randomly assigned to either 10 weeks of Internet-based CBT or to a control group. Self-help material was used in combination with e-mail contact with a personal therapist. Monthly self-ratings of depressive symptoms were made, and diagnostic interviews were conducted before and after the treatment period, as well as 6 months later. RESULTS: Significantly fewer participants in the CBT group experienced relapse (4/38 or 10.5%) compared with those in the control group (14/37 or 37.8%). The difference in relapse rates between groups occurred early in the study period and was still apparent after 6 months. A trend towards a larger reduction in depressive symptoms was observed at post-treatment in the participants who received CBT compared with controls. Reduction in depressive symptoms reduced the risk of relapse. A trend towards a higher remission rate was found in the CBT group at the 6 month follow-up. CONCLUSION: Internet-based CBT seems promising in preventing relapse in persons with partially remitted major depression after previous treatment.