Non-AIDS defining cancers remain a common cause of morbidity and mortality among persons with HIV, and high rates of established risk factors (e.g., tobacco use, oncogenic viral co-infection) have been described among PWH. This study examined data collected through September 2019 from two large, well-characterized U.S. cohorts (Women’s Interagency HIV Study and Multicenter AIDS Cohort Study) to determine whether the effect of smoking on incidence of smoking-related cancers differed by HIV status, if sex modifies impact of risk factors for smoking-related cancers, and the sex-specific attributable risk of smoking. A unique feature of this analysis was availability of information for a highly-similar but HIV-seronegative comparison group. Incidence rates, relative risks, and adjusted population attributable fractions were calculated based on data from 4,423 WIHS and 6,789 MACS participants (representing over 139,500 person-years of follow-up). Investigators observed 214 smoking-related incident cancers among MACS participants and 192 among WIHS participants, with the majority involving the lung/bronchus and diagnosed in the modern ART era (defined as 2001-2018). Age-adjusted incidence rates were significantly higher among PWH than seronegative participants, and were also higher among women versus men. Further, adjusted interaction models demonstrated that effects of cumulative pack-years were significantly stronger in women. Authors estimated that 31% of all smoking-related cancers were attributed to smoking more than 5 pack-years in a lifetime among PWH.