Background: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic morbidity and mortality worldwide, and its epidemiological, clinical, and socioeconomic impact is progressively increasing. A first estimate of the economic burden of COPD in Italy was conducted in 2008 (the SIRIO [Social Impact of Respiratory Integrated Outcomes] study). The aim of the present study is to provide an updated picture of the COPD economic burden in Italy. Methods: Sequential patients presenting at the specialist center for the first time during the period 2008-2012 and with record file complete (demographic, clinical, lung function, and therapeutic data; health care resources consumed in the 12 months before the enrollment and for the 3 subsequent years) were selected from the institutional database. Results: Two hundred and seventy-five COPD patients fitting the inclusion criteria were selected (226 males; mean age: 70.9 years [standard deviation: +/- 8.4 years]; 45.8% were from the north, 25.1% from central Italy, and 29.1% from south Italy). COPD-related average costs per patient in the 12 months before enrollment were as follows: hospitalization: (sic)1,970; outpatient care: (sic)463; pharmaceutical: (sic)499; and indirect costs:(sic)358. Average direct costs and total societal costs were (sic)2,932 and (sic)3,291, respectively. Direct cost was (sic)2,461 (hospitalization: (sic)1,570; outpatient: (sic)344; and pharmaceutical: (sic)547) in the first year of follow-up, while total societal cost was (sic)2,707. No significant difference was reported in any cost category between sexes. Conclusion: The therapeutic approach followed in a specialist center, based on the application of clinical guidelines, has been shown to be a highly effective investment for the long-term management of COPD. A small increase of pharmaceutical costs per year allowed a substantial saving in terms of hospitalizations, costs related to outpatient services, and indirect costs.