Background: Peritoneal carcinomatosis secondary to appendiceal or colorectal cancers is a rare disease marked by short overall and progression-free survival times. Current treatment methods include systemic chemotherapy and cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC), a specialized form of chemotherapy. Predictors of outcome after CRS/HIPEC are largely unknown, especially for patients with high-grade disease. This study examined the effect of systemic chemotherapy and potential prognostic indicators on progression-free survival (PFS) in high-grade peritoneal carcinomatosis patients. Methods: This single center, retrospective cohort study included all patients with high-grade PC of colorectal or appendiceal origin treated with CRS/HIPEC from August 2007 to September 2013. Data were collected from electronic medical records and follow-up continued through January 2014. Survival analysis evaluated associations between PFS and predictor variables including: number of positive lymph nodes (LN), resection status, peritoneal cancer index (PCI), and presence and dose of systemic chemotherapy. Age, sex and primary site of cancer were examined as covariates. Results: A total of 69 patients were included in regression analysis, 41% with appendiceal cancer and 59% with colorectal cancer. Median PFS for the entire cohort was 8.5 months. There was no relationship between PFS and treatment with pre-HIPEC systemic chemotherapy (p=0.51) or the number of treatment cycles (p=0.69). Post-HIPEC (adjuvant) chemotherapy was also not related to PFS (p=.83). Females were more at risk for progression than males, HR 2.16 (1.08-4.33), but not after adjusting for the number of positive LNs. Positive LNs were a significant predictor of PFS both alone and after adjusting for sex, with an adjusted HR of 1.19 (1.08-1.30) for every additional positive node. Conclusions: Even after adjusting for other factors, LN status remained an important predictor of PFS after CRS/HIPEC. LN involvement was significantly related to shorter PFS. The role of systemic chemotherapy remains unclear, though it was not associated with PFS in this cohort.