Background: Type 2 diabetes mellitus is a common, chronic, and costly disease, and its prevalence is increasing in major industrialized countries. Diabetes has indeed a high social impact mainly because of its chronic complications. Objective: The aim of this study was to analyze the direct medical costs attributable to Type 2 diabetes mellitus and its determinants, as assessed in a diabetologic center (DC) in Italy. Methods: We conducted a retrospective longitudinal cost of care study; Type 2 diabetic patients who visited between January 2001 and August 2002 were randomly selected from the database of the DC of Portogruaro. Cost data collected included hospitalizations, visits, diagnostics, and pharmacological therapies and were quantified and analyzed in the perspective of the National Health Service (NHS). Results: Two hundred ninety-nine diabetic patients were extracted, with a mean/patient follow up of 476 days. Mean age was 67.5 years and males represented 67.2% of the sample. The average annual health care cost was found to be o1909.67 per patient; pharmacological therapies accounted for the greatest proportion of direct medical costs (52%), followed by hospitalization (28%) and diagnostic exams (11%). Annual costs increased with the number of diabetes related comorbidities, from o1039 to 3141 per patient in participants with none or more than two complications, respectively. Conclusion: Long-term complications carry a considerable impact on total annual medical cost. Our study demonstrates that an increase in the number of comorbidities is directly associated with an increase of Type 2 diabetes cost. Strategies aimed at preventing the onset of diabetic complications are likely to reduce medical costs in the long run, while improving patients’ health. D 2006 Elsevier Inc. All rights reserved.