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Evidence linking air pollution with adverse health outcomes is accumulating. However, few studies have adopted a quasi-experimental design to evaluate whether decline in air pollution from regulatory action improves public health. We evaluated the effect of a diesel emission control ordinance introduced in 2003 on mortality rates in 23 wards of the Tokyo metropolitan area, Japan, from October 2000 to September 2012, taking into account change in mortality rates in a reference population (Osaka) with a introduction of such a regulation in 2009.We obtained daily counts of all-cause and cause-specific mortality and concentrations of nitrogen dioxide (NO2) and particulate matter less than 2.5 μm in diameter (PM2.5) during the study period. We employed interrupted time-series analysis to analyze the data.Decline in NO2 during the study period was similar in the two areas, while decline in PM2.5 and the improvement in age-standardized mortality rates were greater in Tokyo’s 23 wards compared with Osaka. Even after adjusting for age-standardized mortality rates in Osaka, percent changes in mortality between the first 3-year interval (October 2000 to September 2003) and the last 3-year interval (October 2009 to September 2012) were −6.0% for all causes, −11% for cardiovascular disease, −10% for ischemic heart disease, −6.2% for cerebrovascular disease, −22% for pulmonary disease, and −4.9% for lung cancer. We did not observe a decline in mortality from other causes.This quasi-experimental study in Tokyo suggests that emission control was associated with improvements in both air quality and health outcomes.