Toward the establishment of evidence-based recommendations for the prevention of prostate cancer recurrence after treatment, we examined the association between smoking and prostate cancer recurrence in a retrospective cohort study of 1416 men who underwent radical prostatectomy. Surgeries were performed by a single surgeon at Johns Hopkins Hospital between January 1, 1993, and March 31, 2006. Smoking status at 5 years before and 1 year after surgery was assessed by survey. Prostate cancer recurrence was defined as confirmed re-elevation of prostate-specific antigen levels, local recurrence, metastasis, or prostate cancer death. The cumulative incidence of recurrence was 34.3% among current smokers, 14.8% among former smokers, and 12.1% among never smokers, with a mean follow-up time of 7.3 years. Men who were current smokers at 1 year after surgery were more likely than never smokers to have disease recurrence after adjusting for pathological characteristics, including stage and grade (hazard ratio for recurrence = 2.31, 95% confidence interval = 1.05 to 5.10). This result suggests an association between cigarette smoking and risk of prostate cancer recurrence.