OBJECTIVE: To evaluate the impact of air pollution on hospitalizations for respiratory and cardiovascular diseases in the largest Brazilian metropolis. METHODS: This study was carried out at the Metropolitan Region of São Paulo, Brazil. Environmental data were obtained from the network of monitoring stations of nine municipalities. Air pollution exposure was measured by daily means of PM10 (particles with a nominal mean aerodynamic diameter ≤ 10 μm) per municipality, while daily counts of hospitalizations for respiratory and cardiovascular diseases within the Brazilian Unified Health System were the outcome. For each municipality a time series analysis was carried out in which a semiparametric Poisson regression model was the framework to explain the daily fluctuations on counts of hospitalizations over time. The results were combined in a meta-analysis to estimate the overall risk of PM10 in hospitalizations for respiratory and cardiovascular diseases at the Metropolitan Region of São Paulo. RESULTS: Regarding hospitalizations for respiratory diseases, the effect estimates were statistically significant (p < 0.05) for all municipalities, except Santo André and Taboão da Serra. The RR (Relative Risk) of this outcome for an increase of 10 µg/m3 in the levels of PM10 ranged from 1.011 (95%CI 1.009–1.013) for São Paulo to 1.032 (95%CI 1.024–1.040) in São Bernardo do Campo. The RR of hospitalization for respiratory diseases in children for an increase of 10 µg/m3 of PM10 ranged from 1.009 (95%CI 1.001–1.017) in Santo André to 1.077 (95%CI 1.056–1.098) in Mauá. Only São Paulo and São Bernardo do Campo presented positive and statistically significant results for hospitalizations for cardiovascular diseases. CONCLUSIONS: This is the first study to estimate the risk of illness from air pollution in the set of municipalities of the Metropolitan Region of São Paulo, Brazil. Global estimates of the effect of exposure to pollution in the region indicated associations only with respiratory diseases. Only São Paulo and São Bernardo do Campo showed an association between the levels of PM10 and hospitalizations for cardiovascular diseases.