Long-term outcomes of a randomized experiment (BIOPEX) compare biological mesh and primary perineal closure in rectal cancer patients following extralevator abdominoperineal resection and prior radiation, primarily focusing on a symptomatic perineal hernia. This was a posthoc secondary analysis of patients randomized to biological mesh closure (n=50; 2 dropouts) or primary perineal closure (n=54; 1 dropout) in the BIOPEX trial. Patients were monitored for 5 years. The Kaplan-Meier statistic was used to calculate actuarial 5-year probabilities. Actuarial 5-year symptomatic perineal hernia rates after biological mesh closure were 7% (95% CI, 0–30) versus 30% (95% CI, 10–49) after primary closure (P=0.006). In the biomesh group, one patient (2%) had an elective perineal hernia repair, compared to 7 patients (13%) in the primary closure group (P=0.062). Small intestinal blockage necessitated reoperation in 1/48 patients (2%) and 5/53 patients (9%), respectively (P=0.208). Chronic perineal wound issues, locoregional recurrence, overall survival, and the key categories of quality of life and the functional outcome showed no significant variations. After biological mesh closure, the rate of symptomatic perineal hernia after abdominoperineal resection for rectal cancer decreased at a 5-year follow-up. Closure with a biological mesh did not affect the quality of life or functional outcomes.