Anal cancer is one of the most common cancers affecting human immunodeficiency virus (HIV)-infected male patients. Currently, there is no consensus on posttreatment surveillance of HIV-infected men who have sex with men (MSM) who have been treated for high-grade intraepithelial neoplasia (HGAIN), the likely precursor to anal cancer. The aim of this study was to assess the cost-effectiveness of a range of strategies for anal cancer surveillance in HIV-infected MSM previously treated for HGAIN. We developed a Markov model to project quality-adjusted life expectancy, lifetime costs, and the incremental cost-effectiveness ratios of 5 strategies using high-resolution anoscopy (HRA) and/or anal cytology testing after treatment. Performing HRA alone at 6- and 12-month visits was associated with a cost-effectiveness ratio of $4446 per quality-adjusted life year gained. In comparison, combined HRA and anal cytology at both visits provided greater health benefit at a cost of $17,373 per quality-adjusted life year gained. Our results were robust over a number of scenarios and assumptions including patients' level of immunosuppression. Results were most sensitive to test characteristics and cost, as well as progression rates of normal to HGAIN and HGAIN to cancer. Our results suggest that combined HRA and anal cytology at 6 and 12 months may be a cost-effective surveillance strategy after treatment of HGAIN in HIV-infected MSM.