BACKGROUND: One-third of patients with peritoneal carcinomatosis undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) present alterations in conventional coagulation test results. However, perioperative coagulation has not been systematically investigated in these patients. This study aimed to investigate hemostatic changes in such patients. METHODS: This prospective observational study included patients with peritoneal carcinomatosis who underwent CRS-HIPEC. Variables of conventional coagulation and rotational thromboelastometry (ROTEM) parameters of patients who underwent CRS-HIPEC at baseline (time 0, T0: before surgery) were compared with those of healthy blood donors (HBD). Blood samples were collected at baseline (T0), 2-h (T2), and 72-h (T72) after surgery. RESULTS: 44 patients who underwent CRS-HIPEC and 40 HBDs were included. At T0, patients who underwent CRS-HIPEC presented with lower hemoglobin levels and elevated C-reactive protein, fibrinogen, factor XIII (FXIII), and D-dimer levels than HBDs. At T2, significant decreases in hemoglobin, platelet count, fibrinogen, and FXIII levels were observed. In contrast, D-dimer and von Willebrand factor levels increased. Regarding ROTEM parameters, in the postoperative period, increased clotting time in thromboelastometry with extrinsic activation, and maximum clot firmness in thromboelastometry with fibrin contribution, along with a significant decrease in maximum clot firmness in thromboelastometry with extrinsic activation without a hyperfibrinolysis pattern, were observed. Platelet function, as assessed using the platelet function assay, was normal. CONCLUSIONS: CRS-HIPEC causes coagulopathy secondary to a pronounced platelet drop, worsening of fibrinogen and FXIII levels, and impaired clot firmness as evidenced by ROTEM. A proinflammatory status was ubiquitously observed.