Evidence suggests that smoking may have negative associations with HIV health outcomes. The smoking rate in our sample of people living with HIV (N = 333) was triple that of the general population (57 v. 19 %). Regression analyses revealed that (smokers v. non-smokers) reported lower medication adherence (unstandardized beta = 9.01) and were more likely to have a detectable viral load (OR = 2.85, 95 % CI [1.53–5.30]). Smokers attended fewer routine medical visits (β = −0.16) and were more likely to report recent hospitalization (OR = 1.89, 95 % CI [0.99, 3.57]). Smokers ranked “health” as less important to their quality of life (β = −0.13) and were more likely to report problematic alcohol (OR = 2.40, 95 % CI [1.35, 4.30]), cocaine (OR = 2.87, 95 % CI [1.48–5.58]), heroin (OR = 4.75, 95 % CI [1.01, 22.30]), or marijuana use (OR = 3.08, 95 % CI [1.76–5.38]). Findings underscore the need for integrated behavioral smoking cessation interventions and routine tobacco screenings in HIV primary care.