Purpose: Despite trials demonstrating its efficacy, many physicians harbor concerns regarding the use of natalizumab in the treatment of patients with refractory Crohn's disease (CD). The purpose of this study was to perform a descriptive analysis of a series of CD patients not enrolled in a clinical trial who received natalizumab (N). Methods: Patients on N were identified from the following five sites in Massachusetts: Boston Medical Center, Brigham and Women's Hospital, Lahey Clinic, Massachusetts General Hospital and UMass Medical Center. A retrospective chart review was performed to collect demographic data, disease characteristics, medications used prior to initiation of N and duration of N use. Results: 33 patients on N were identified, of whom 75% were female and 90% were white. The average age (± SD, range) at the start of N was 36 years (± 12, 21-66), by which time patients had CD for an average of 10.6 years (± 6.5, 2-22). 73% had ileocolonic disease, 17% had colonic disease, and 10% ileal disease. In addition, 11 patients had upper GI involvement and 6 had perianal disease, 3 of whom had diverting ileostomies. Other prior surgeries were bowel resection (60% of all patients) and fistula repair (36%). Prior non-biologic therapies were steroids (100%), 6MP/AZA (91%), antibiotics (66%) and methotrexate (52%). All but one patient with a history of optic neuritis, had tried and failed anti-TNF agents: 8 failed 3, 18 failed 2 and 6 failed 1. Of the 33 patients identified, 7 patients did not respond to induction therapy (after 3-4 infusions), 6 stopped due to loss of efficacy (after 11-14 infusions), 6 had an allergic reaction (half after 2 infusions and half after > 10 infusions) and 2 stopped due to patient request or noncompliance. 13 were maintained on N with an average of 12.5 (± 11.7, 2-39) infusions. Duration of active treatments was < 1 year for 4 patients, 1-2 years for 1 patient and > 2 years (4 patients). Adverse events included herpes zoster, headaches, vertigo, low back pain, rash, and abdominal abscess. No case of progressive multifocal leukoencephalopathy was observed. Conclusion: Natalizumab is not widely used in our centers. In our clinical experience outside clinical trials, it is largely reserved for CD patients with extensive ileocolonic disease associated with upper GI and perianal disease who have failed conventional immunosuppressants and at least two anti-TNF agents. However, this drug is well tolerated and offers significant clinical improvement for more than 1 year in one-third of these difficult-to-treat CD patients. Drs. Wasan and Juillerat equally participated as first authors of this abstract. Disclosure: Dr. Joshua Korzenik-Advisory Board, Elan.