Chronic graft-versus-host disease (GVHD) is a major limitation of successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photochemotherapy (ECP) has been tested extensively in small cohorts of patients with chronic GVHD. In this study, we retrospectively evaluated 71 patients with severe chronic GVHD treated with ECP. Response rate was 61% (n = 43), and 14 patients had complete responses (CRs). The best responses were observed in skin, liver, oral mucosa, and eye. Factors affecting outcomes were assessed in the less heavily pretreated subgroup (n = 63). Thrombocytopenia was associated with a lower response rate (P = .04), and there was a trend toward a higher response rate in de novo chronic GVHD. At 6 months, a total of 27 (69%) of 39 patients who were alive continued to have a sustained response (CR 4 [10%] of 39, and partial response [PR] 23 [59%] of 39). The cumulative incidence of steroid discontinuation at 1 year was 22%. The overall survival since initiation of therapy was 53% at 1 year. Response to ECP and platelet count at initiation of therapy were the strongest predictors of nonrelapse mortality (NRM) on univariate analysis. Objective responses were observed in a substantial number of patients with both skin and visceral chronic GVHD failing corticosteroids and other immunosuppression.