The role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with extraperitoneal disease (EPD) is controversial. Among patients with peritoneal metastases from appendiceal cancer (AC) and colorectal cancer (CRC) who underwent CRS-HIPEC, those with EPD (liver, lung, or retroperitoneal lymph nodes [RP LN]) were retrospectively compared to those without EPD. Overall (OS) and recurrence-free survival (RFS) analyses were performed before/after propensity score matching (PSM). Among 1341 patients with AC (64%) or CRC (36%) who underwent CRS ± HIPEC, 134 (10%) had EPD whereas 1207 (90%) did not. EPD was located in the lungs (47%), RP LN (28%), liver (18%), or multiple (6%). Patients with EPD experienced worse median OS (34 versus 63mo; P=0.002) and RFS (12 versus 19mo; P<0.001). On a multivariable analysis, EPD was associated with worse RFS (P=0.003), but not OS (P=0.071). After PSM, the association of EPD with OS (P=0.204) and RFS (P=0.056) was no longer significant. In the multivariable analysis of the PSM cohort, EPD was not associated with OS (P=0.157) or RFS (P=0.110). The findings of this large retrospective multi-institutional study suggest that EPD alone, while a negative prognostic indicator, should not be considered an absolute contraindication to CRS ± HIPEC for otherwise well-selected patients with peritoneal surface malignancies. Further research is needed to delineate whether location of EPD influences OS and RFS following CRS-HIPEC.