Introduction: Ustekinumab is a fully human IgG1κ monoclonal antibody that blocks the p40 subunit of interleukin-12/23, inflammatory cytokines implicated in the pathogenesis of Crohn's disease (CD). Ustekinumab is approved for treatment of plaque psoriasis. It was reported to be effective for induction and maintenance of clinical response in anti-TNF resistant CD only Aim: To describe a real-life experience with open -label use of subcutaneous ustekinumab in anti-TNF resistant CD patients, in a tertiary referral center setting. Methods: A retrospective observational study. Clinical response was defined by physician's global assessment combined with decision to continue therapy. Clinical endpoints were over 12 months of follow-up or discontinuation of ustekinumab. The primary outcome was clinical response by 3 months. Secondary outcomes included clinical response at 6 and 12 months and steroid-free response at each time-point. Results: Patient characteristics: 37 patients were treated with subcutaneous ustekinumab between 2/2011 to 7/2013 (median follow up: 5 (3-12) months). The demographic and clinical characteristics of the patients were as follows: male50%, age37 (21-62), age at diagnosis20.5 (2-54) years. The disease characteristics were as follows: location ileal 16.2% , colonic 18.9%, ileocolonic 64.9%; disease phenotype: luminal 46%; penetrating 43.2%, structuring 10.8%; 40.5% had perianal involvement; 27.5% had previously undergone total proctocolectomy. Previous treatment included at least one biologic in all patients, two biologics in 86.7% and three biologics in 18.9 %. A loading dose was administered in 89% of the patients: 90 mg at weeks 0,1,2 80%; 45 mg at weeks 0 and 4 -12% , 90 mg at weeks 0 and 4 8% of the patients. Initial maintenance dosing included: 90 mg q8 wk73%, 90 mg q4 wk -21.6% , 45/ 90 mg q12wk 12 5.2% of the patients. The mean duration of follow-up was 6.1 ± 3.9 months. Follow-up data was available for 37, 24 and 16 patients at 3, 6, and 12 months, respectively. Treatment outcomes: Clinical response at 3 months was achieved in 22/37 (59.5%) of the patients; 11 (50%) of these patients were steroid-dependent at treatment onset, 7/11 (63.6%) were able to discontinue corticosteroids and 18.2% to decrease the dose by at least 50%. At 6 months, among the 15 patients with follow-up data available 11 (73%) were still responsive; 3 additional patients were non-responders at 3 months but responded at 6 months. At 12 months, follow-up data was available for 9/25 of earlier responders; 6/9 (66%) maintained their response; all were steroid-free. Summary: In this cohort of severe anti-TNF resistant CDpatients, initial response to subcutaneous ustekinumab resulted in clinical response in almost 60% of patients, with the majority of responders sustaining the benefit for 6-12 months.