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Background: Studies suggest volatile anesthetics and opioids may enhance the malignant potential of cancer cells. The objective of this single institution retrospective study was to evaluate the survival impact of a multimodal opioid-sparing nonvolatile anesthetic technique (MA) in a group of patients who had undergone cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) for appendiceal carcinomatosis. Methods: Propensity score matching (PSM) and Cox proportional hazard models were used to compare the survivals of patients who received MA (MA group), to those who received volatile-opioid anesthesia (volatile-opioid group). Results: Of the 373 patients, 110 (29%) were in the MA group and 263 (71%) in the volatile-opioid group. The MA group was older (mean ± standard deviation (SD): 55 ± 11 versus 53 ± 10 years, p ¼ .035) and had more patients with ASA scores 3 or 4 (90% versus 81%, p ¼ .032), and those with high grade tumors (18% versus 12%, p ¼ .009). Intraoperative opioid consumption was lower in the MA group (mean morphine equivalents ± SD: 13 ± 10 versus 194 ± 789, p < .0001). After PSM, 107 patients remained in each group. In the adjusted Cox proportional hazards model after PSM, MA was not associated with improved progression free survival (PFS) (HR 1.45, 95% CI [0.94-2.22], p ¼ .093) or overall survival (OS) (HR 1.66, 95% CI [0.86-3.20], p ¼ .128), when compared to volatile-opioid anesthesia. Conclusions: In this retrospective study, a multimodal opioid-sparing nonvolatile anesthetic approach was not associated with improved survival. Precis' statement: In this study of patients undergoing major cancer surgery, the use of multimodal anesthetic and analgesic agents, while avoiding volatile anesthetics and minimizing opioid use was not associated with improved survival. ARTICLE HISTORY