Background: Prevalence of HIV, smoking, and pulmonary infections in South Africa are high.Objectives: We investigated the role of smoking and HIV status on lung function.Methods: This is a secondary analysis of a cross-sectional study conducted in South Africa. Data included demographics, pulmonary risk factors and a spirometry test to obtain the forced expiratory volume in one second (FEV1) and the ratio of FEV1/forced vital capacity (FVC). In the initial multivariable regression analysis, the effect of smoking on pulmonary function in HIV-positive adults was assessed. The analysis was repeated, assessing the influence of HIV status on lung function in both HIV-negative and HIV-positive smokers. The models were adjusted for age, sex, body mass index (BMI), time since HIV diagnosis, antiretroviral treatment (ART) use, occupational hazards, history of tuberculosis or pneumonia, indoor smoking and the presence of an indoor fireplace during childhood.Results: This study included 524 people living with HIV (PLWH, 66.7% female, mean age 40.9 years [s.d.; 9.4]) and 79 HIV-negative smokers (77.2% male, mean age 34.4 years [s.d.: 12.1]). Of the PLWH, 118 (22.5%) were past or current smokers and 406 (77.5%) were non-smokers. Smoking was not associated with changes in the FEV1 or FEV1/FVC ratio in multivariable regression analysis. In the second analysis, HIV status was also not associated with reduced pulmonary function following adjustment for confounders.Conclusion: Neither smoking nor being HIV-positive was associated with decreased pulmonary function in this relatively young population. These findings should be confirmed in a longitudinal study, including an older population.