Cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC) increases survival in peritoneal carcinomatosis, but complications may affect the long-term prognosis. We aimed to evaluate the postoperative evolution after CS + HIPEC, the appearance of adverse outcomes, and the associated risk factors. This was a retrospective observational study evaluating clinical practice in patients undergoing CS + HIPEC from 2016 to 2023 in a tertiary-level university hospital. The pre-, intra-, and postoperative variables were collected. The postoperative evolution, the appearance of postoperative complications, and the mortality were analyzed according to the perioperative data. In total, 62.3% of the patients developed some kind of complication. Renal failure was related to the length of surgery [mean difference (md) 111 min, 95% CI 11-210, = 0.029], postoperative vasoactive support [Odds Ratio (OR) 3.4, 95% CI 1.1-10.6, = 0.033], and non-invasive mechanical ventilation (OR 5.5, 95% CI 1.5-20.5, = 0.007). Respiratory failure was associated with renal replacement therapies (OR 13.8, 95% CI 1.3-143.9, = 0.006), postoperative creatinine (md 0.27 mg·dL, 95% CI 0.1-0.4, = 0.001), and C-reactive protein (md 33.5 mcg·L, 95% CI 0.1-66.8, = 0.049). Infectious complications were related to the length of surgery (md 84 min, 95% CI 12-156, = 0.024), non-invasive mechanical ventilation (OR 4.4, 95% CI 1.2-16.1, = 0.018), and renal replacement therapies (OR 11.6, 95% CI 1.1-119.6, = 0.012). The hospital stay was longer in patients with complications (md 14.8 ± 5.5 days, 95% CI 3.8-25.8, = 0.009). The mortality rate at 12 months was 15.6%. The mortality risk factors were the preoperative hemoglobin (md -1.7 g·dL, 95% CI -2.8--0.7, = 0.001) and creatinine (md -0.12 mg·dL, 95% CI -0.21--0.04, = 0.007) and the postoperative hemoglobin (md -1.15 g·dL, 95% CI 0.01-2.30, = 0.049) and C-reactive protein (md 54.6 mcg·L, 95% CI 18.5-90.8, = 0.004). Intraoperative epidural analgesia was found to be a protective factor for 12-month mortality (OR 0.25, 95% CI 0.07-0.90 = 0.027). A multivariate analysis performed after a univariate analysis showed that the only risk factor for overall mortality was not using intraoperative epidural analgesia. CS + HIPEC led to a high incidence of postoperative complications, but the occurrence of complications did not seem to affect postoperative survival.