OBJECTIVE:With combination-antiretroviral therapy, HIV-infected individuals live longer with an elevated burden of cancer. Given the high prevalence of smoking among HIV-infected populations, we examined the risk of incident cancers attributable to ever smoking cigarettes. DESIGN:Observational cohort of HIV-infected participants with 270 136 person-years of follow-up in the North American AIDS Cohort Collaboration on Research and Design consortium. Among 52 441 participants, 2306 were diagnosed with cancer during 2000–2015. MAIN OUTCOME MEASURES:Estimated hazard ratios and population-attributable fractions (PAF) associated with ever cigarette smoking for all cancers combined, smoking-related cancers, and cancers that were not attributed to smoking. RESULTS:People with cancer were more frequently ever smokers (79%) compared with people without cancer (73%). Adjusting for demographic and clinical factors, cigarette smoking was associated with increased risk of cancer overall hazard ratios = 1.33 (95% confidence interval1.18–1.49); smoking-related cancers hazard ratios = 2.31 (1.80–2.98); lung cancer hazard ratios = 17.80 (5.60–56.63); but not nonsmoking-related cancers hazard ratios = 1.12 (0.98–1.28). Adjusted PAFs associated with ever cigarette smoking were as followsall cancers combined, PAF = 19% (95% confidence interval13–25%); smoking-related cancers, PAF = 50% (39–59%); lung cancer, PAF = 94% (82–98%); and nonsmoking-related cancers, PAF = 9% (1–16%). CONCLUSION:Among HIV-infected persons, approximately one-fifth of all incident cancer, including half of smoking-related cancer, and 94% of lung cancer diagnoses could potentially be prevented by eliminating cigarette smoking. Cigarette smoking could contribute to some cancers that were classified as nonsmoking-related cancers in this report. Enhanced smoking cessation efforts targeted to HIV-infected individuals are needed.