Chronic pulmonary diseases are a major cause of morbidity and mortality worldwide. The present study is a case-control study nested in a defined cohort, undertaken in Athens, Greece, in order to investigate the association between long-term exposure to ambient air pollution and the development of chronic bronchitis, emphysema or chronic obstructive pulmonary disease (COPD). Individualized personal exposure assessment has been applied based on long-term residential and occupational subject history linked with geographical air pollution distribution. The first consecutive 3904 participants from the European Prospective Study into Cancer and Nutrition (EPIC), all residents of Athens, were asked to complete a questionnaire. One hundred and sixty-eight participants reporting a history of COPD symptomatology and 168 healthy controls recruited from the same study base individually matched for age and gender, were visited by a physician at their homes for conducting spirometry and a medical interview. Eighty-four of the 168 self-identified as cases were diagnosed as having chronic bronchitis, emphysema or COPD. Logistic regression models were used for statistical evaluation. Cases were more exposed to air pollution compared to controls. The estimated odds ratio (OR) indicates an increase of 37% in the risk of medically confirmed cases per exposure quartile (p = 0.02). When most of the subjects exposed are considered vs. all others, there is a twofold increase in disease risk (p = 0.03). Our findings provide evidence that long-term exposure to air pollution is an important factor in the development of chronic respiratory diseases.