Infliximab has shown promising results for the treatment of severe psoriasis and may be considered in patients who are unresponsive to conventional systemic and biologic therapy. We conducted a retrospective study of 19 patients treated with infliximab for severe psoriasis who had previously been treated with etanercept. These patients had recalcitrant plaque psoriasis, which was unresponsive to multiple conventional systemic therapies before treatment with etanercept. Patients were evaluated for side effects and response to therapy. Nineteen patients (men = 14, women = 5) with a mean age of 50 years (range 34-83) were included in this study. Fourteen patients (74%) lost response after an initial improvement with etanercept, 3 had to discontinue because of insurance issues, and two failed to respond. Two of the 19 patients (11%) experienced infections while receiving etanercept. After the initiation of infliximab therapy, 17 of 19 patients (89%) showed initial improvement after 12 to 14 weeks, based on the physician's global assessment and body surface area done by a single physician. Ten patients (53%) required infliximab dose escalation to maintain control of their disease. Fifteen patients (79%) still receive infliximab therapy with favorable disease control. For these patients, the median time for treatment is 8 months (range 4-25). One patient experienced a minor infusion reaction and preferred not to continue after two infusions. Nine patients experienced minor infections. Two patients with known coronary artery disease died of myocardial infarction. This was a retrospective study at a single practice site. Infliximab was effective in patients with psoriasis previously treated with etanercept, but the majority of patients required infusions every 6 weeks to maintain their continued response. In addition, the use of infliximab was associated with a possible increased incidence of adverse events.