Abdominoperineal resection is associated with significant morbidity. The perineal wound poses a unique risk and complications are common, including skin breakdown, abscess, sinus tracts, perineal herniation, and evisceration. A 2-component fibrin sealant made from pooled human plasma has been proven to achieve hemostasis and tissue sealing. We report a case series of 5 consecutive patients in whom we used this fibrin sealant during perineal wound closure. Of our patients, 2 patients (40%) were diabetic and 4 patients (80%) received preoperative radiotherapy. The median body mass index was 32 (calculated as weight in kilograms divided by height in meters squared). The patients were at increased risk of perineal wound dehiscence and infection. Median follow-up was 6 months, and no patients had perineal wound complications. A fibrin sealant could be used as an alternative to more invasive procedures, such as flap reconstruction, in patients at high risk of perineal wound dehiscence.