Summary. Background: Consistent evidence has indicated that air pollution increases the risk of cardiovascular diseases. The underlying mechanisms linking air pollutants to increased cardiovascular risk are unclear. Objectives: We investigated the association between the pollution levels and changes in such global coagulation tests as the prothrombin time (PT) and the activated partial thromboplastin time (APTT) in 1218 normal subjects from the Lombardia Region, Italy. Plasma fibrinogen and naturally occurring anticoagulant proteins were also evaluated. Methods: Hourly concentrations of particulate (PM10) and gaseous pollutants (CO, NO2, SO2, and O3) were obtained from 53 monitoring sites covering the study area. Generalized additive models were applied to compute standardized regression coefficients controlled for age, gender, body mass index, smoking, alcohol, hormone use, temperature, day of the year, and long-term trends. Results: The PT became shorter with higher ambient air concentrations at the time of the study of PM10 (coefficient = −0.06; P < 0.05), CO (coefficient = −0.11; P < 0.001) and NO2 (coefficient =−0.06; P < 0.05). In the 30 days before blood sampling, the PT was also negatively associated with the average PM10 (coefficient = −0.08; P < 0.05) and NO2 (coefficient = −0.08; P < 0.05). No association was found between the APTT and air pollutant levels. In addition, no consistent relations with air pollution were found for fibrinogen, antithrombin, protein C and protein S. Conclusions: This investigation shows that air pollution is associated with changes in the global coagulation function, suggesting a tendency towards hypercoagulability after short-term exposure to air pollution. Whether these changes contribute to trigger cardiovascular events remains to be established.