Background. Depression is highly prevalent in Western countries and is associated with increased health care costs. Most depressed patients are treated in primary care. Objective. To estimate the resource use and costs of depressed patients treated in primary care in comparison with matched controls. Methods. Data from an electronic medical record system of 20 general practices in The Netherlands for the years 2002–04 were used. A patient was considered depressed when having a diagnosis of depression and either a prescription for antidepressants or a referral to mental health care. Matching was based on age, sex and GP. Multilevel analyses combined with bootstrapping were performed to compare costs between depressed and matched control patients while correcting for clustering at the level of the GP and adjusting for confounding by age, sex and co-morbidity. Results. The prevalence of recognized and subsequently treated depression was 3.1% [95% confidence interval (CI) 3.0 to 3.2]. Total health care costs per patient in 2002–04 were on average €2859 (SD 2297) in depressed patients and €658 (SD 1070) in control patients (mean difference €2202, 95% CI 2146 to 2257). After adjustment for co-morbidity, depressed patients had excess costs of €1403 (95% CI 1350 to 1456). Conclusion. Our results show that health care costs of depressed patients are much higher compared with matched controls even after adjusting for co-morbidity. This was not only true for mental but also for general medical care utilization. These results emphasize the need to develop cost-effective interventions to treat depression in primary care.