Surgical management of anal fistulas in Crohn's disease (CD) is associated with high failure rates, and treatment options are limited due to ongoing proctitis, multiple tracts, and concern for incontinence and non-healing wounds. The aim of this study was to investigate the healing rate of ligation of the inters-sphincteric fistula tract (LIFT) for anal fistulas in Crohn's disease and identify prognostic factors for healing. This prospective analysis compared long-term healing rates of CD patients undergoing LIFT for anal fistulas. Consecutive patients with CD who underwent LIFT procedure at our institution, in the period from March 2012 to September 2019 were included. The main outcome was anal fistula healing rate. The study cohort of 46 patients (mean age of 34.2 ± 13.0years, 18 (40%) males). After a mean follow-up time of 33 ± 28months, fistula healing was seen in 30 (65%) patients. A total of 8 patients were noted to have inter-sphincteric recurrence and 8 patients had trans-sphincteric recurrence. Smoking at the time of surgery was significantly associated with LIFT failure (HR 3.18, 95% CI 1.18-8.61, p = 0.02). Other factors, such as age, sex, race, disease duration and location, type of fistula history of proctitis, preoperatively use of biologics or a seton, and previous repair attempts, did not appear to influence LIFT healing. Although not statistically significant, there was a trend toward increase in failure among patients with active proctitis at the time of surgery (HR 1.97, 95% CI 0.71-5.42, p = 0.19). Our increasing experience with LIFT for anal fistula in CD demonstrates a higher rate of healing (65%) than previously reported (48%). Smoking appears to negatively influence healing of LIFT in CD.