BACKGROUND: Ligation of the intersphincteric fistula tract is a sphincter-preserving technique for the treatment of anal fistulas. The BioLIFT modification involves the placement of a biologic mesh in the intersphincteric plane. Advocates of this modification state improved healing rates, however evidence for this is lacking, and this approach costs significantly more. OBJECTIVE: The purpose of this study was to compare the healing rates of the ligation of the intersphincteric fistula tract with the BioLIFT. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted at a tertiary care hospital from April 2008 to April 2018. PATIENTS: All adult patients with transsphincteric anal fistulas were included. Patients were excluded if they had IBD, more than 1 fistula tract operated on simultaneously, or a previous attempt at repair. MAIN OUTCOME MEASURES: The primary outcome was primary healing of the fistula tract, and secondary outcomes included overall success, complications, and time to recurrence. RESULTS: There were 119 cases (75 ligation of the intersphincteric fistula tract and 44 BioLIFTs). One surgeon performed 84% of the BioLIFT cases. The primary healing rate was 75.0% versus 58.7% (p = 0.08), and the complication rate was 22.7% versus 17.3% (p = 0.48; BioLIFT vs ligation of intersphincteric fistula tract). After multivariate logistic regression, the BioLIFT had a significantly better healing rate (OR = 2.38 (95% CI, 1.01-5.62); p = 0.048). Median follow-up was 9 versus 29 weeks (BioLIFT vs ligation of intersphincteric fistula tract). Kaplan-Meier analysis demonstrated no difference in the time to recurrence (p = 0.48). LIMITATIONS: This study was limited by the retrospective nature, different lengths of follow-up, and varying case numbers between the surgeons. CONCLUSIONS: The BioLIFT modification is safe and effective for the treatment of anal fistulas but has a higher cost. This modification warrants additional prospective studies to establish its benefits over the ligation of the intersphincteric fistula tract procedure.