<jats:title>Abstract</jats:title><jats:p> <jats:bold>Background</jats:bold> </jats:p><jats:p>Extracorporeal photochemotherapy (photopheresis), an immune‐modulating therapy, has been demonstrated to elicit a therapeutic response in the treatment of several autoimmune disorders. We evaluated the use of photopheresis in the treatment of patients with progressive systemic sclerosis (PSS; scleroderma).</jats:p><jats:p> <jats:bold>Methods</jats:bold> </jats:p><jats:p>Five patients with early‐onset, diffuse PSS were treated with photopheresis on 2 successive days monthly for an average of 59 months (range 54–69 months). We initially reported the response this group of patients had to photopheresis treatment at an average of 11 months (range 6–21 months).</jats:p><jats:p> <jats:bold>Results</jats:bold> </jats:p><jats:p>An improvement or stabilization was noted in most patients in skin thickening, joint mobility, pulmonary function studies, oral aperture, functional index, as well as symptoms including Raynaud's phenomenon, dyspnea, fatigue, dysphagia, arthralgias, and cutaneous ulcers. Renal function tests remained within normal range. A total of 296 monthly treatments were administered without significant toxicity.</jats:p><jats:p> <jats:bold>Conclusions</jats:bold> </jats:p><jats:p>This study suggests that extended use of extracorporeal photochemotherapy in the management of early‐onset, diffuse PSS is well tolerated and may provide an increasingly beneficial clinical outcome.</jats:p>