Background <p>Comprehensive smoke-free policies are necessary to protect South African adolescents against second-hand smoke exposure. This study aims to estimate the prevalence of second-hand smoke and identify factors associated with exposure to second-hand smoke among adolescents. This study also assesses factors responsible for adolescents’ female-male gap in exposure to second-hand smoke.</p> Methods <p>Global Youth Tobacco Survey (GYTS) data was used to estimate the second-hand smoke prevalence. Participants comprised 6287 never-smoking adolescents. Chi-Square tests and modified Poisson regression analyses were conducted to identify factors associated with adolescents’ second-hand smoke exposure. Fairlie’s decomposition technique was applied to understand the relative contribution of different covariates to the female-male gap in second-hand smoke.</p> Results <p>Overall, 39.7% of all never-smoking South African adolescents reported exposure to second-hand smoke at home and/or in places other than home. By specific location, the prevalence of second-hand smoke exposure at home and in places other than home was 22.2% and 32.8%, respectively. Second-hand smoke was related to age, grade, and smoking parents or guardians, according to modified Poisson regression models. The data also suggest that the proportion predicting second-hand smoke exposure is 44.56% for females and 37.85% for males, resulting in a 6.71% gender gap. Tobacco advertisement was the most significant contributor to the gender disparity in second-hand smoke exposure.</p> Conclusion <p>Second-hand smoke exposure is still prevalent among South African adolescents. This necessitates a full discussion of strategies aimed at reducing second-hand smoke exposure. Effective smoke-free policies for the home and public areas should be devised and properly enforced.</p>