Background: The costs and side effects of several antiandrogen therapies for advanced prostate cancer differ substantially. We estimated the cost-effectiveness of antiandrogen therapies for advanced prostate cancer. Methods: We performed a cost-effectiveness analysis using a Markov model based on a formal meta-analysis and literature review. The base case was assumed to be a 65-year-old man with a clinically evident, local recurrence of prostate cancer. The model used a societal perspective and a time horizon of 20 years. Six androgen suppression strategies were evaluated: diethylstilbestrol (DES), orchiectomy, a nonsteroidal antiandrogen (NSAA), a luteinizing hormone-releasing hormone (LHRH) agonist, and combinations of an NSAA with an LHRH agonist or orchiectomy. Outcome measures were survival, quality-adjusted life years (QALYs), lifetime costs, and incremental cost-effectiveness ratios. Results: DES, the least expensive therapy, had a discounted lifetime cost of $3600 and the lowest quality-adjusted survival, 4.6 QALYs. At a cost of $7000, orchiectomy was associated with 5.1 QALYs, resulting in an incremental cost-effectiveness ratio of $7500/QALY relative to DES. All other strategies—LHRH agonists, NSAA, and both combined androgen blockade strategies—had higher costs and lower quality-adjusted survival than orchiectomy. These results were sensitive to the quality of life associated with orchiectomy and the efficacy of combined androgen blockade, and they changed little when prostate-specific antigen results were used to guide therapy. Under a wide range of other assumptions, the cost-effectiveness of orchiectomy relative to DES was consistently less than $20 000/QALY. Androgen suppression therapies were most cost-effective if initiated after patients became symptomatic from prostate metastases. Conclusions: For men who accept it, orchiectomy is likely to be the most cost-effective androgen suppression strategy. Combined androgen blockade is the least economically attractive option, yielding small health benefits at high relative costs.