BACKGROUND: Healing rates after surgical closure for high perianal fistula in patients with Crohn's disease are even more disappointing than in patients with cryptoglandular fistulas. The objective was to improve healing rates by combining the well-known mucosal advancement flap with platelet-rich plasma. METHODS: A prospective pilot study was conducted in one tertiary referral centre. Consecutive patients with primary or recurrent Crohn's disease-related high perianal fistulas, defined as involving the middle and/or upper third parts of the anal sphincter complex, were included. A staged procedure was performed with non-cutting seton treatment for 3 months first, followed by a mucosal advancement flap with injection of platelet-rich plasma into the fistula tract. RESULTS: Ten consecutive patients were operated on between 2009 and 2014. Half (50 %) of the patients had undergone previous fistula surgery. Mean follow-up was 23.3 months (SD 13.0). Healing of the fistula was 70 % (95 % confidence interval, 33-89 %) at 1 year. One (10 %) patient had a recurrence, and in two (20 %) patients, the fistula was persistent after treatment. An abscess occurred in one (10 %) patient. The median post-operative Vaizey score was 8.0 (range 0-21), indicating a moderate to severe continence impairment. CONCLUSIONS: The results of combining the mucosal advancement flap with platelet-rich plasma in patients with Crohn's disease-related high perianal fistulas are moderate with a healing rate of 70 %. Further investigation is needed to determine the benefits and risks on continence status for this technique in this patient population.