Objective: Depression is an increasing common mental disorder associated with significant costs for both patients and health care systems. The aim of this study was to assess the overall direct costs of depression for 2004 in the Local Health Authority n.9 (LHA9), Treviso, Italy. Methods: Data were retrieved from the database of pharmaceutical prescriptions including all prescriptions reimbursed by the National Health Service (NHS). In this retrospective cohort study, patients were enrolled with a depression diagnosis from a psychiatrist (DSM cohort) or treated with one of the following antidepressant drugs: tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI) and other antidepressants (SFT cohort). If they had any prescription of antidepressant in the previous 2 years they were considered prevalent patients, otherwise they were recognized as incident. Results: Antidepressants were prescribed to 13,984 patients: females and males were the 4.8% and 2.2% of the total population living in LHA9, respectively. The total of direct costs for depressive illness, including drugs (antidepressants and all other drugs), hospital admissions, and laboratory analyses, was € 37,174,107.13, where hospital admissions represented the 42.7%. The cost/year of the SFT cohort for prevalent patients was € 2,438; whereas that of incident patients was € 4,022 vs € 2,792 before and after starting the antidepressant treatment, respectively. The same pattern, but with higher values of cost, was observed in the DMS cohort. Conclusions: Cost/year after the beginning of antidepressant therapy or for prevalent patients was lower than that for incident patients, because the former exhibited a decrease in hospitalization. © 2007 Adis Data Information BV.