ABSTRACT: The aim of this study was to compare the cost-effectiveness and quality-adjusted life years (QALYs) of active monitoring (AM), radical prostatectomy (PR), and external-beam radiotherapy with neoadjuvant hormone therapy (RT) for localized prostate cancer. Microsimulations of radical prostatectomy, 3D-conformal radiotherapy, or active monitoring were performed using Medicare reimbursement schedules and clinical trial results for a target population of men aged 50-69 years with newly diagnosed localized prostate cancer (T1-T2, NX, M0) over a time horizon of 10 years. Quality-adjusted life years (QALYs) and costs were assessed and sensitivity analyses performed. Monte Carlo simulations revealed that the mean cost for AM, PR, and RT were $15,654, $18,791, and $30,378, respectively, and QALYs were 6.96, 7.44, and 7.9 years, respectively. The incremental cost-effectiveness ratio (ICER) was $6,548 for PR over AM and $68,339 for RT over PR. Results were sensitive to the number of years of follow-up and procedure cost. With relaxed assumptions for AM, the ICER of PR and RT met the societal willingness to pay (WTP) threshold of $50,000 per QALY. Compared with AM, PR was highly cost-effective. RT and PR for localized prostate cancer can be cost-effective, but RT must offer increased QALYs or decreased procedural costs to be cost-effective compared to PR. Newer and cheaper radiotherapy strategies like stereotactic body radiotherapy may play a crucial role in future early prostate cancer management.