Adults aging with HIV infection are at risk for age-related comorbidities and syndromes, such as frailty. The objective of this study was to evaluate the expression and predictors of the frailty phenotype (FP) among HIV-infected (HIV+) and HIV-uninfected (HIV-) men who have sex with men. A prospective, observational cohort study was nested in the Multicenter AIDS Cohort Study from October 2007-September 2011. FP conversion was defined as the onset of FP over two consecutive study visits. Adjusted odds ratios and 95% confidence intervals (,) for FP conversion were estimated using logistic regression models with generalized estimating equations. Of 10,571 completed study visits from 1,946 men who have sex with men, 12% and 9% were FP+ among HIV+ and HIV- men, respectively (p = .002). The proportion of FP+ visits increased with age regardless of HIV status, but was significantly greater in HIV+ compared to HIV- men aged 50-64 years. Of the 10,276 consecutive visit pairs contributed by participants, 5% (537) were classified as FP conversion, and 45% of the men with FP conversion had only one FP+ study visit. FP conversion was significantly associated with a history of AIDS (adjusted odds ratios = 2.26 1.50, 3.39, but not with HIV+ alone (adjusted odds ratios = 1.26 0.98, 1.64). Among men who had one or more FP+ visits, 34% of HIV+ and 38% of HIV- men had less than two comorbidities. These findings suggest that expression of the FP can be measured in men who have sex with men with and without HIV infection and reflects multisystem dysfunction in this population; further investigations are needed to better understand clinical utility.