OBJECTIVES: To investigate the efficacy, effectiveness and safety of etanercept, a soluble tumour necrosis factor-alpha receptor, in a prospective observational cohort of patients with refractory psoriatic arthritis and polyarticular involvement. METHODS: Twenty patients with psoriatic arthritis refractory to conventional anti-rheumatic drugs were treated with etanercept 25 mg subcutaneously twice a week for 26 weeks. Efficacy and safety were recorded at weeks 2, 6, 10, 16, 20 and 26. Effectiveness, defined as clinical remission, reduction of 50% in clinical parameters and concomitant NSAID use, was evaluated at 26 weeks. RESULTS: Etanercept therapy was efficacious in this cohort as 85% of the patients met the Psoriatic Arthritis Response Criterion at week 26. Effectiveness of etanercept for the individual patient was demonstrated, since at least 50% of the patients had a 90 and 85% improvement in swollen and tender joint count, respectively, and a 71% improvement in the Health Assessment Questionnaire at week 26. Four patients showed complete remission and NSAIDs were stopped in 10/15 patients. The most common adverse events were upper respiratory tract infections. Interestingly, in two patients psoriasis worsened during the study, unrelated to the course of arthritis. The administration of etanercept was interrupted in three patients for adverse events: one septic bursitis, one myocardial infarction and one tooth abscess. After resolution of the adverse events, etanercept was successfully reintroduced. CONCLUSIONS: Etanercept in monotherapy is efficacious, effective and safe in the majority of patients with refractory psoriatic arthritis.