Because of air quality management and control, traffic-related air pollution has declined in Quito, Ecuador. We evaluated the effect of a city-wide 5-year air pollution control program on the occurrence of acute respiratory illness (ARI). We compared two studies conducted at the same location in Quito: in 2000, 2 years before the policy to control vehicle emission was introduced, and in 2007. Each study involved ~ 730 children aged 6-12 years, observed for 15 weeks. We examined associations between carboxyhemoglobin (COHb) serum concentration-an exposure proxy for carbon monoxide (CO)-ambient CO, and ARI in both cohorts. In 2007, we found a 48% reduction in the ARI incidence (RR 0.52; 95% CI 0.45-0.62, p < 0.0001), and 92% decrease in the percentage of children with COHb > 2.5% as compared to the 2000 study. We found no association between COHb concentrations above the safe level of 2.5% and the ARI incidence (p = 0.736). The decline in air pollution due to vehicle emissions control was associated with a lower incidence of respiratory illness in school children.