Background Gastrointestinal perforation (GIP) is a rare complication after adult liver transplant (LT) associated with high morbidity and mortality. Limited data are available about clinical risk factors and underlying pathogenic mechanisms. Methods The retrospective study included all GIP cases from a consecutive cohort of 361 LT recipients during the period 2005-2017. Clinical variables were investigated as potential risk factors for GIP, and radiologic and histopathologic evaluations were undertaken to identify any causative mechanism. Results A total of 22 patients developed at least 1 episode of GIP (prevalence 6.1%) at a median time of 18.5 [interquartile range, 12.5-28.5] days after LT. The perforations occurred in the small bowel (63.6%), transverse colon (27.3%), right colon (22.7%), left colon (9.1%), and stomach (9.1%). A total of 27.3% of patients developed multiple sites of GIP, and in 31% GIP recurred after curative surgery. The 30-day mortality rate after relaparotomy was 40%. A history of previous abdominal surgery (odds ratio, 2.5) and early post-LT relaparotomy due to other complications (odds ratio, 2.6) were significant risk factors for GIP. No thromboembolic or steno-occlusive complications of any splanchnic vessel were detected at computed tomography scan, while histopathology examination on perforated gastrointestinal segments excluded cytomegalovirus infection, graft-vs-host disease, and inflammatory bowel disease. In all the cases, ischemic necrosis with aspecific microangiopathy and microembolization were the pathologic features detected. Conclusions GIP is a severe complication after LT with frequent multiple gastrointestinal involvement and recurrence after curative surgery. The pathologic underlying mechanism is usually microvascular ischemia. Clinical risk factors are history of previous abdominal surgery and early post-LT relaparotomy.