This work have like purpose quantitative estimates of the short-term effects of air pollution on the health of residents of five municipalities of the Metropolitan Area of Guadalajara, Mexico from 2012 to 2015 using time-series approach. Air Quality was assessed for CO, NO2, SO2, O3 and PM10. Tlaquepaque had the highest mean concentrations for CO (0.88 ppm), NO2 (24.55 ppb), SO2 (0.0036 ppm) and PM10 (53.81 µg m–3), whereas, Zapopan registered the highest mean value for O3 (25.06 ppb). Only PM10 and Ozone exceeded the maximum permissible values established in the Mexican official standards. SO2 presented the highest RRI values in MAG, especially for Zapopan and Tonala, for the majority of the population: 0–59 years and > 60 years. Regarding to CO, excepting Guadalajara and Tlaquepaque, associations were not significant in the most of studied municipalities. The increase of risk as percentage for NO2 was 1.77% for 0–59 years in Guadalajara and Tlaquepaque, 1.87% by respiratory causes in Tlaquepaque, 1.73% > 60 years in Tonala, and 1.25% for 0–59 years in Zapopan. The association between daily mortality and increased O3 levels were significant, however, values were low for all studied municipalities. Finally, regarding to PM10, only Zapopan and Tonala showed statistical significance. This study cannot predict if reductions in criteria pollutants levels would have an important effect on a reduction in daily mortality, however, considering the large size of population exposed, even when observed associations were small but significant, RRI values found are of public concern.