Background: Information on longer-term safety andtolerability is needed to confidently prescribe alefacept therapy for chronic plaque psoriasis beyond 1 or 2 courses. Objective: The aim of this work was to further examine the safety profile of alefacept by integrating data from clinical trials involving patients with chronic plaque psoriasis who received up to 9 courses of therapy over a 5-year period. Methods: Data from 13 clinical trials conducted in patients with plaque psoriasis were integrated because they had similar inclusion/exclusion criteria and assessments. Patients who enrolled in the analyzed trials were aged ≥15 years with chronic plaque psoriasis for ≥12 months that involved ≥10% of body surface area, and CD4+ Tlymphocyte counts above the lower limit of normal (>404 cells/μL). The incidences of adverse events (AEs), serious AEs, discontinuations for AEs, infections, serious infections, malignancies, and anti-alefacept antibodies were summarized for each course of alefacept. The incidence of infections was stratified according to CD4+ Tlymphocyte counts (<250 cells/μL vs ≥250 cells/μL). Results: Data from 13 clinical trials of alefacept were integrated and summarized (multicenter, randomized, double-blind studies, n = 6; multicenter, open-label studies, n = 5; other, n = 2). The analyzed population (n = 1869) included 1291 (69.1%) men and 578 (30.9%) women, between the ages of 15 and 84 years (mean, 44.8 years), of whom 1648 (88.2%) were white. Weights ranged from 40 kg to 206 kg (mean, 90.0 kg). A total of 1369 of these patients had been included in a previous analysis. Among the most commonly reported AEs in each treatment course were headache (0%–14.2%), nasopharyngitis (7.7%–25.0%), influenza (0%–8.1%), upper respiratory tract infection (0%–12.5%), and pruritus (0%–7.5%). The rates of discontinuations due to AEs (0%–4.8%), serious AEs (0%–4.8%), serious infections (0%–0.9%), or malignancies (0%–4.8%) did not appear to increase with repeated exposure. Fewer than 1 % of patients in each course developed a serious infection. No opportunistic infections or infection-related deaths were reported. The incidence of infections appeared to be unrelated to CD4+ Tlymphocyte counts. Fewer than 2.5% of patients tested positive for anti-alefacept antibodies during any course of therapy. Conclusions: This integrated analysis of data from13 trials with 1869 patients supports the safety and tolerability of alefacept for longer-term treatment of psoriasis.