Background/Aim: In sub-Sahara Africa, few studies have investigated the short-term association between hospital admissions and ambient air pollution. Therefore, this study explored the association between multiple air pollutants and hospital admissions in Cape Town, South Africa. Methods: Generalized additive quasi-Poisson models were used within a distributed lag linear modelling framework to estimate the cumulative effects of PM10, NO2, and SO2 up to a lag of 21 days. We further conducted multi-pollutant models and stratified our analysis by age group, sex, and season. Results: The overall relative risk (95% confidence interval (CI)) for PM10, NO2, and SO2 at lag 0–1 for hospital admissions due to respiratory disease (RD) were 1.9% (0.5–3.2%), 2.3% (0.6–4%), and 1.1% (−0.2–2.4%), respectively. For cardiovascular disease (CVD), these values were 2.1% (0.6–3.5%), 1% (−0.8–2.8%), and −0.3% (−1.6–1.1%), respectively, per inter-quartile range increase of 12 µg/m3 for PM10, 7.3 µg/m3 for NO2, and 3.6 µg/m3 for SO2. The overall cumulative risks for RD per IQR increase in PM10 and NO2 for children were 2% (0.2–3.9%) and 3.1% (0.7–5.6%), respectively. Conclusion: We found robust associations of daily respiratory disease hospital admissions with daily PM10 and NO2 concentrations. Associations were strongest among children and warm season for RD.