Background: Extracorporeal photopheresis (ECP) involves ex vivo leukocyte treatment with methoxsalen and UVA light to generate a tolerogenic response. A previous trial demonstrated that ECP permits corticosteroid withdrawal in steroid-dependent Crohn's disease (CD) patients who were in clinical remission. We studied the effect of ECP on steroid withdrawal in steroid-dependent CD. Methods: Patients with CD for $6 months, in remission at baseline while on steroids, but who had failed at $1 steroid withdrawal were included. Patients received two ECP treatments every 2 weeks for the 24-week steroid tapering period and underwent steroid-tapering. Patients completing steroid tapering could receive maintenance ECP (two treatments/week) every month for 24 weeks. Results: Thirty-one patients (Crohn's Disease Activity Index [CDAI] score 91; Inflammatory Bowel Disease Questionnaire [IBDQ] 172.5) were enrolled (baseline corticosteroid dose, 20 mg/day); 65% were refractory to/intolerant of anti-tumor necrosis factor (TNF) agents or immunosuppressants. After 24 weeks of ECP, 7 of 31 (22.6%) patients discontinued steroids while maintaining a CDAI of ,150. At week 24, the steroid dose for the remaining patients on corticosteroids was 10 mg (P , 0.003 vs. baseline) with a CDAI of 110 and an IBDQ of 179. Following maintenance treatment, three patients remained in steroid-free remission. The 10 patients in the study and receiving ECP at week 48 had a steroid dose of 3.5 mg with a CDAI of 40 and an IBDQ of 188. Conclusions: ECP permitted discontinuation or reduction of steroids in a population of refractory steroid-dependent CD patients. ECP may be useful in permitting steroid withdrawal in selected steroid-dependent CD patients. Ideally, these results need to be confirmed in a "sham-controlled" clinical trial. Copyright © 2013 Crohn's & Colitis Foundation of America, Inc.