The aim of this study was to evaluate the efficacy and tolerability of high-dose escitalopram in patients suffering from obsessive–compulsive disorder (OCD). In an open-label, 16-week prospective study, patients with OCD received escitalopram at a dose of 20 mg/day for 3 weeks, after a 1-week titration at 10 mg/day. Patients who did not achieve a ≥25% reduction from baseline in the Yale–Brown Obsessive Compulsive Scale (Y-BOCS) score during these 4 weeks were continued on higher doses of escitalopram (maximum 50 mg/day) for 12 weeks. The primary efficacy measure of OCD symptoms was change from baseline in the Y-BOCS score. Overall, 67 patients (33 women, 34 men) with a mean Y-BOCS score of 29.6 entered the study. After 4 weeks of standard-dose escitalopram treatment, one patient discontinued owing to pregnancy, and two patients achieved a reduction in Y-BOCS ≥25%. Consequently, 64 patients were eligible to receive high-dose escitalopram (mean dose, 33.8 mg/day at endpoint). At endpoint, high-dose escitalopram had significantly improved the OCD symptoms (Y-BOCS score) and all the other efficacy measures (P<0.001), compared with baseline. Escitalopram was also well tolerated, with no discontinuations during the 12-week high-dose phase. The only reported adverse drug reactions were dry mouth (n=8, 12.1%) and decreased sexual desire (n=21, 31.8%). Preliminary investigation shows that high-dose escitalopram is an efficacious and well tolerated treatment for patients suffering from severe OCD. Randomized, blinded studies are needed to reinforce these findings.