OBJECTIVES Intermediate-risk prostate cancer patients are recommended primary treatment with either radical prostatectomy (RP), external beam radiotherapy (EBRT), brachytherapy (BT),  or EBRT plus high-dose rate BT boost (EBRT + HDR-BT); or expectant management with active surveillance (AS). The costs of these treatments differ considerably, whilst the amount and quality of evidence for their comparative effectiveness in terms of disease progression, adverse events and health-related quality of life is unbalanced and inconclusive. Therefore, we undertook a cost-effectiveness analysis of RP, EBRT, BT, EBRT + HDR-BT and AS, and performed a value-of-information analysis to direct future research. METHODS We developed a probabilistic Markov model estimating the expected incremental cost/(Quality Adjusted) Life Years from a UK-NHS perspective, with a time horizon of 10 years. Input data were obtained from the best available literature. We explored the uncertainty around the model outcomes by identifying the most influential parameters and estimating the expected value of perfect (parameter) information.   RESULTS AS is most likely to be cost-effective at a cost/QALY threshold (λ) < ₤3,000/QALY, BT for λ ₤3,000 to ₤12,000/QALY and RP for λ >₤12,000/QALY. One-way sensitivity analysis shows that utilities and probabilities of adverse events are main effect drivers and initial treatment costs are main cost drivers. Large decision uncertainty exists around λ ₤11,000 with a population EVPI of nearly ₤100 million. The EVPPI suggests that eliminating uncertainty around costs and utilities is most worthwhile. CONCLUSIONS With current information AS and BT are cost-effective treatments for intermediate-risk prostate cancer at relatively low cost/QALY thresholds, and RP is expected to be the most cost-effective of available treatments at the prevailing range of cost/QALY thresholds (i.e. ₤20,000-₤30,000) . However, large decision uncertainty exists and acquiring further information is likely cost-effective. Future research on costs and utilities associated with treatment outcome and adverse events is expected to be most valuable.