Background: Major depression is a world-wide problem that can be treated with various forms of psychotherapy. There is strong research support for treating major depression using cognitive behavior therapy delivered in the format of guided self-help via the Internet (ICBT). Recent research also suggests that psychodynamic psychotherapy can be delivered as guided self-help via the Internet (IPDT) and that it seem to be as effective as ICBT for mild to moderate depression. However, no head-to-head comparison between the two treatments exists. In the field of Internet interventions it is largely unexplored if treatment preference affects outcome and adherence. Methods: Participants were allocated to IPDT or ICBT based on their stated preference. More than half of the participants preferred ICBT (N = 30) over IPDT (N = 14). Differences in efficacy between treatments were explored. Correlations between strength of preference and treatment outcome, adherence to treatment and completion of the whole treatment program were explored. Data were collected before and after treatment, as well as in a 7-month follow-up. Results: During the treatment period, both programs performed equally well in reducing symptoms. More participants who received IPDT completed the entire program. At follow-up, mixed-effects models showed that participants who chose ICBT improved more in terms of quality of life. The ICBT group also had a significant increase in participants who recovered from their depression from post-treatment to follow-up. Exploratory analyses indicated that strength of preference was correlated with adherence to treatment and completion of the whole program, and long-term outcome for the ICBT group. Conclusions: Few differences were found during the acute treatment phase, but the long-term effects are in favor of ICBT. Strength of preference for treatment seems to have a predictive value. Further research comparing the efficacy of ICBT and IPDT, and the effects of preference matching and strength of preference, is warranted.Trial registration: This trial is a continuation of the study registered as NCT01324050 at Clinicaltrials.gov.