Background <p>Most patients who have colorectal cancer peritoneal metastases (CRC-PM) treated with cytoreductive surgery ± hyperthermic intraperitoneal chemotherapy (CRS±HIPEC) experience recurrence within 1&#xa0;year. This study assessed the safety and oncologic value of secondary CRS±HIPEC for patients with CRC-PM.</p> Methods <p>A multi-institutional database of patients treated for CRC-PM (2000–2024) was reviewed. Patients who underwent curative-intent initial CRS±HIPEC alone were compared with those who underwent secondary CRS±HIPEC for recurrent disease. Patients who received more than two procedures were excluded. The primary objective was to evaluate the safety of secondary CRS±HIPEC for CRC-PM as measured by perioperative outcomes. The secondary objective was to examine the association between overall survival (OS) and secondary CRS±HIPEC.</p> Results <p>The study included 136 patients, 17 of whom underwent secondary CRS±HIPEC. There was no difference in postoperative complications between secondary and initial CRS±HIPEC. When OS was defined from the date of the index operation, secondary CRS±HIPEC was associated with improved OS versus initial CRS±HIPEC alone (51.0 months [95% confidence interval {CI}, 39.8–62.2 months] vs. 24.0 months [95 % CI, 19.4–28.6) months]). To assess the value of secondary CRS±HIPEC, OS was compared from the date of the second procedure for the secondary cohort. Overall survival measured after secondary CRS±HIPEC was similar to that after initial CRS±HIPEC (27.0 months [95 % CI, 17.3–36.7 months] vs. 24.0 months [95 % CI, 19.4–28.6 months]). Among the patients with recurrence after their index CRS±HIPEC, secondary CRS±HIPEC remained associated with better OS than that of those who received only one procedure (27.0 months [95 % CI, 17.3–36.7 months] vs. 12.0 months [95 % CI, 9.2–14.8 months]).</p> Conclusion <p>Secondary CRS±HIPEC should be considered for well-selected patients with CRC-PM recurrence.</p>