BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has become the treatment of choice for resectable peritoneal carcinomatosis (PC) and improved the survival of these patients. The situation changes if PC recurs and repeated CRS with HIPEC is considered. The patient selection and outcome of the repeated approach has not been well described. We analyzed our cohort and share the experiences. METHODS: Ninety-three CRS/HIPEC procedures, performed in 85 patients during the period 2001-2013, were examined in a retrospective analysis. Type of primary, ECOG status, peritoneal cancer index (PCI), completeness of cytoreduction (CC), duration of hospitalization, postoperative morbidity, mortality, and disease-free/overall survival were reviewed. RESULTS: Six patients (7%) underwent a second CRS/HIPEC (median interval between the two procedures: 26 months, range 8-61) including two patients with mesotheliomas, one patient with ovarian adenocarcinoma, one patient with leiomyosarcoma of uterus, one patient with colon adenocarcinoma, and one patient with appendiceal adenocarcinoma. The last two patients underwent a third CRS/HIPEC, 25 and 36 months, after the second procedure. The median PCI was 14 (range, 4-26) during the first and 20 (range, 7-39) during the second CRS/HIPEC of these patients. Completeness of cytoreduction score of 0 (CC-0) was achieved in all first procedures and in 67% of second procedures (CC-0; n=4 and CC-1; n=2). A CC-0 score was possible in both of the third procedures. The mean operating time was 444 min (range, 198-642) and 427 min (range, 239-617) during the first and the second procedure. Median intensive care unit (ICU) was 2 days, and hospital stay after second CRS/HIPEC was 17 days (range, 7-50). The 30-day morbidity after repeated CRS/HIPEC was 33% (16% for grade III-IV complications), and there was no 30-day mortality neither after the second nor after the third CRS/HIPEC. Median disease-free interval between first CRS/HIPEC and peritoneal recurrence was 17 months (range, 8-30). Median disease-free survival of 18 months (range, 4-33) was achieved after the second CRS/HIPEC. After a median follow-up of 74 months (range, 39-151), all patients are alive with disease (n=5) or disease free (n=1) under chemotherapy. CONCLUSIONS: In experienced centers, repeated CRS/HIPEC can be performed with safety. Patient selection and correct timing is of particular importance in achieving control of the disease. Repeated CRS/HIPEC should be considered as treatment option for selected patients with recurrent PC.