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The purpose of this study was to compare the ligation of intersphincteric fistula tract (LIFT) with an additional plug (LIFT-plug) in the treatment of transsphincteric anal fistula.Both LIFT and LIFT-plug are recently reported effective alternatives of transsphincteric anal fistula.This multicenter prospective randomized study (NCT01478139) was conducted at 5 university hospitals throughout China. A total of 235 patients were randomly assigned to undergo LIFT (118 patients) or LIFT-plug (117 patients) between March 2011 and April 2013. The primary outcome measured was primary healing rate at 6 months postoperatively and healing time. Secondary outcomes included recurrence rate, postoperative pain, and incontinence rate.The LIFT procedure showed shorter operative time than the LIFT-plug procedure (26.7 min vs 28.5 min, P = 0.03). Median healing time was 22 days in LIFT-plug group vs 30 days in LIFT group (P < 0.001). The difference in visual analog scale scores across all time points was not statistically significant between the groups (P = 0.13). The primary healing rate was higher in LIFT-plug group than in LIFT group [94.0% (95% confidence interval 89.7%–98.3%) vs 83.9% (95% confidence interval 77.2%–90.6%), P < 0.001]. There were no reported incontinence and recurrence within the follow-up period of 6 months.In patients with transsphincteric anal fistulas, both LIFT-plug and LIFT are simple, safe, and effective procedures. LIFT-plug has the advantage of a higher healing rate, less healing time, and a lower early postoperative pain score.