: Peritoneal relapse after cytoreduction and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is common. Repeat CRS/HIPEC offers the potential for long-term survival in the appropriately selected patient. : We performed a retrospective review of a single institution database to assess perioperative outcomes after repeat CRS/HIPEC for appendiceal (pAC) and colorectal (pCRC) cancers. Kaplan-Meier and Cox estimates were used to assess survival. : Of 157 patients, 103 patients underwent initial CRS/HIPEC for pAC ( = 67) or pCRC ( = 36) histologies. Twenty-seven pAC patients (27/67, 40%) and 23/36 pCRC patients (63%) developed disease recurrence. Relapsed patients had a higher burden of disease (PCI), operative length and blood loss and received adjuvant chemotherapy (all < 0.05). Nine of the 27 relapsed pAC patients and 5 of the 13 relapsed pCRC patients underwent repeat CRS/HIPEC. The median time to repeat CRS/HIPEC was 18 months (4-26 months), and a CCR-0 and CCR-1 were achieved in 79% and 21%, respectively. The 1-, 3- and 5-year OS for pAC patients who underwent repeat CRS/HIPEC was 88.9%, 88.9% and 77.8%, and the 1- and 3-year OS for pCRC patients was 100% and 25%, respectively. Repeat CRS/HIPEC for pAC was associated with significant improvement in OS ( = 0.03), while for pCRC, no significant difference was observed ( = 0.99). : Repeat CRS/HIPEC for isolated peritoneal recurrence is safe and offers the potential for long-term survival. Patient selection is key to ensure optimal cytoreduction when considering repeat CRS/HIPEC.