Anal fistula treatment remains a surgical challenge. This study focuses on the efficiency and safety of the Ligation of Intersphincteric Fistula Tract (LIFT) procedure for high intersphincteric anorectal fistulas, aiming to identify prognostic factors for success and complications. A retrospective chart review was conducted on all patients who underwent LIFT procedure at a tertiary referral hospital between January 2013 and January 2021. The primary endpoint was the success rate of fistula closure, confirmed with clinical investigation. Secondary endpoints included postoperative complications, reintervention and self-reported incontinence. Logistic regression analyses were performed for assessing prognostic factors for fistula closure and postoperative complications. Ninety-two patients were included in the study; after a median follow-up of 19.3 months, fistula closure was achieved in 71% (n = 65) and in 89% (n = 82) after reinterventions. 46% (n = 42) reported persistent symptoms, although 83% of which (n = 32/42) had succesful fistula tract closure by clinical evaluation. One patient developed incontinency for gas. Smoking emerged as a significant risk factor for fistula closure failure, OR = 6.75, 95% CI = [1.65, 27.69], p = 0.030. Wound dehiscence was the most common complication, occuring in 25% (n = 23). Prolonged oral antibiotics demonstrated a significant protective effect against wound dehiscence, OR = 0.31, 95% CI = [0.10, 0.96], p = 0.036. The LIFT procedure is an efficient and safe treatment for complex perianal fistula. Patient satisfaction emerged as a crucial treatment goal, as patients can remain symptomatic after fistula closure. Emphasizing smoking cessation is integral to the treatment approach. The findings suggest prolonged antibiotic treatment as a potential preventive measure for wound dehiscence.