The prevalence of depression and anxiety is higher in patients with stroke than in the general population but it is unclear whether patients with stroke are at an increased risk of being treated for depression and anxiety compared with patients with other chronic illness. The objective of the present study was to investigate whether the rate of treatment with antidepressants is increased in patients with stroke compared with patients with other chronic illness and compared with the general population. By linkage of nationwide case registers, all patients who received a main diagnosis of stroke or osteoarthritis at their first ever admission or first outpatient contact during the period from 1995 to 2001 in Denmark were identified, and the rates of subsequent purchase of antidepressants were calculated. In total, 9,999 patients with a main first diagnosis of stroke and 12,127 patients with a main first diagnosis of osteoarthritis were included. In all, 23.6% of patients with stroke and 9.1% of patients with osteoarthritis purchased antidepressants during follow-up. Patients who received a first diagnosis of stroke had a 3.44 (95% confidence interval: 3.19-3.70) times increased rate of subsequently purchasing antidepressants compared with patients with a first diagnosis of osteoarthritis. The rate was increased in all subgroups of patients regardless of sex, age, socioeconomic group and time since diagnosis. Furthermore, the rate of treatment was greater than the rate among a sex, age and calendar-matched sample of the general population. It is concluded that stroke is associated with an increased rate of antidepressant treatment in clinical practice regardless of sex, age, socioeconomic group and time since diagnosis.