Abstract Introduction Given that people living with HIV (PLWH) are disproportionately burdened by tobacco-related morbidity and mortality, it is critically important to understand the degree to which evidence-based cessation interventions are utilized by and are effective among PLWH. Aims and Methods This secondary data analysis aimed to examine differences in Quitline treatment enrollment and 6-month cessation outcomes among smokers seeking care at 1 HIV clinic and 12 non-HIV clinics that were part of a large healthcare system in the greater Houston, Texas metropolitan area, United States. Data were from a 34-month (April 2013–February 2016) one-group implementation trial that evaluated the Ask-Advise-Connect (AAC) approach to linking smokers with Quitline treatment. Primary outcomes included (1) treatment enrollment and (2) 6-month self-reported and biochemically confirmed abstinence. Results The smoking status of 218 915 unique patients was recorded in the electronic health record; 5285 (2.7%) of these patients were seen at the HIV clinic where the smoking prevalence was 45.9%; smoking prevalence at the non-HIV clinics was 17.9%. The proportion of identified smokers who enrolled in treatment was 10.8% at the HIV clinic and 11.8% at the non-HIV clinics. The self-reported abstinence rate was 18.7% among HIV clinic patients and 16.5% among non-HIV clinic patients. Biochemically confirmed abstinence was lower at 4.2% and 4.5%, respectively (all ps > .05). Conclusions AAC resulted in rates of Quitline treatment enrollment and abstinence rates that were comparable among patients seen at an HIV clinic and non-HIV clinics. Findings suggest that AAC should be considered for widespread implementation in HIV clinics. Implications PLWH were as likely as other patients to enroll in evidence-based tobacco cessation treatment when it was offered in the context of a primary care visit. Cessation outcomes were also comparable. Therefore, standard care for PLWH should include routine screening for smoking status and referrals to cessation treatment.