Background: Treatment-resistant depression (TRD) accounts for a large fraction of the burden of depression. The interventions currently used are mostly pharmacological and short-term psychotherapies, but their effectiveness is limited. The Tavistock Adult Depression Study found evidence for the effectiveness of long-term psychoanalytic psychotherapy (LTPP) plus treatment as usual (TAU), versus TAU alone, for TRD. Even after a 2-year follow-up, moderate effect sizes were sustained. This study assessed the cost-effectiveness of this LTPP + TAU. Methods: We conducted a within-trial economic evaluation using a Bayesian framework. Results: Quality-adjusted life years (QALYs) were 0.16 higher in the LTPP + TAU group compared with TAU. The direct cost of LTPP was £5500, with no substantial compensating savings elsewhere. Overall, average health and social care costs in the LTPP + TAU group were £5000 more than in the TAU group, employment rates were unchanged, and effects on other non-healthcare costs were uncertain. Accordingly, the incremental cost-effectiveness ratio was ≈£33,000/QALY; the probability that LTPP + TAU was cost-effective at a willingness to pay of £20,000/QALY was 18 %. Limitations: The sample size of this study was relatively small, and the fraction of missing service-use data was approximately 50 % at all time points. The study was conducted at a single site, potentially reducing generalizability. Conclusions: Although LTPP + TAU was found to be clinically effective for treating TRD, it was not found to be cost-effective compared with TAU. However, given the sustained effects over the follow-up period it is likely that the time horizon of this study was too short to capture all benefits of LTPP augmentation.