Background: As methotrexate (MTX) is a widely used treatment for psoriasis, it is important to gain insight into the reasons for the discontinuation of MTX and to understand the determinants for drug survival. Objectives: To describe 5-year drug survival for MTX in patients with psoriasis, split according to different reasons for discontinuation, and to identify the determinants for drug survival. Methods: Data were extracted from a prospective psoriasis registry of patients treated with MTX (MTX-CAPTURE). Drug survival was analysed using Kaplan–Meier estimates and the determinants for discontinuation were analysed using Cox regression analysis. Analyses were split according to the reason for discontinuation: side-effects or ineffectiveness. Results: We included 85 patients treated with MTX, with a maximum treatment duration of 5·2 years. The overall drug survival rates were 63%, 30% and 15% after 1, 3 and 5 years, respectively. The median survival was 1·8 years. Overall, 55 patients (65%) discontinued MTX for the following reasons: side-effects (35%), ineffectiveness (26%), combination of side-effects and ineffectiveness (13%), other reasons (16%) and 11% were lost to follow-up. The most reported side-effects were gastrointestinal symptoms, despite the use of folic acid in 99% of patients. Based on univariate analysis, a high Psoriasis Area and Severity Index score and a high score on the visual analogue scale for disease severity at baseline were possible determinants for a short drug survival. Conclusions: Drug survival of MTX was low with 15% of patients ‘on drug’ after 5 years. Side-effects alone or in combination with inadequate disease control were more important in the context of treatment discontinuation than inadequate disease control alone.