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Background: Study identify individual effect of single pollutants on asthma acute exacerbation (AE) may overlook the health effect of the mixture overall. In real world, dynamic changes of air pollutants and meteorologic factors coexist simultaneously. A comprehensive study was carried out to examine the influence of air pollution and meteorologic factors on asthma AE. Materials and methods: The asthma AE data from emergency room visits were collected from the Taiwan National Health Insurance Research Database from 2005 to 2013. Complete monitoring data for the air pollutants (sulfur dioxide, SO2; nitrogen dioxide, NO2; ozone, O3; carbon monoxide, CO; PM2.5; and PM10) and meteorologic factors (relative humidity, rainfall, and daily average temperature) were collected from Environmental Protection Agency monitoring stations. A bi-directional case-crossover analysis was used to investigate the effects of air pollution and meteorological factors on asthma exacerbation. Result: Along age group divisions, a 1 ℃ temperature increase was a protective factor for asthma ER visits, with OR = 0.981 (95% CI 0.971–0.991) and 0.985 (95% CI, 0.975–0.994) for pediatric and young adult patients, respectively. Each 1 mg/m3 increase in the 48-h averages of PM2.5 was associated with asthma ER visit for patients older than 65 years of age (OR = 1.008 (95% CI, 1.003–1.014). Conclusion: In Taiwan, asthma AE is closely related to low temperature and certain air pollution. Patients can take appropriate protective strategies to minimize risk of asthma AE related to air pollution/meteorological factors according to relevant gender and age.