<p>Tobacco and cannabis use are prevalent among adults with HIV and co-use is associated with drug dependence and negative health outcomes such as lung disease. This study examined the co-use of tobacco and cannabis by HIV status overall and by sociodemographics. Data came from the adult sample from the 2021–2023 National Survey on Drug Use and Health. Adjusted multinomial logistic regressions were performed on tobacco cannabis co-use by HIV status, adjusting for covariates. We tested potential interaction effects between HIV status and each sociodemographic factor (i.e., age, sex, race/ethnicity, income, state-level medical cannabis legalization status) on the outcome. Among total adult respondents (<i>N</i> = 139,524), 0.4% (weighted) reported lifetime HIV diagnosis and 8.2% reported past-month tobacco and cannabis co-use. After adjusting for covariates, adults with HIV, compared with adults without HIV, were more likely to report past-month tobacco and cannabis co-use (aRRR = 3.35, 95% CI = 1.79, 6.27). We also observed that race/ethnicity and state-level medical cannabis legalization status modified the association between HIV diagnosis and tobacco and cannabis co-use. This study observed a higher prevalence of tobacco and cannabis co-use among adults with HIV overall and identified subgroup sociodemographic differences by race/ethnicity and state-level medical cannabis legalization.</p>