Objective To investigate the risk factors of intraoperative blood loss in patients undergoing supratentorial tumor resections. Methods This was a single‑center retrospective cohort study. Clinical data were collected from 310 patients who were scheduled for supratentorial tumor resection from July 2018 to June 2019 (203 cases were eventually enrolled). The patients were divided into two groups depending on whether the intraoperative blood loss was more than 500 ml: a blood loss >500 ml group (n=42) and a blood loss ≤500 ml group (n=161). Both groups were compared for baseline information before surgery, anesthetic and operative information, intraoperative rapid thromboelastography (r‑TEG), postoperative complications, the length and cost of hospitalization stay. The logistic regression analysis was performed to predict the related factors of blood loss >500 ml. Results Patients with blood loss >500 ml showed higher percentages of meningioma, World Health Organization (WHO) grade Ⅰ‒Ⅱ, anterior cranial fossa space‑occupying lesions, tumor invasion, maximum diameter tumor ≥4 cm, tumor partial resection and operation duration >240 min than those with blood loss ≤500 ml (P<0.05). Univariate logistic regression analysis showed that the above variables were correlated with blood loss >500 ml (P<0.05). Furthermore, multivariate logistic regression showed that the maximum diameter tumor ≥4 cm [odds ratio (OR)=4.21, 95%CI 1.52‒11.71], meningioma (OR=9.05, 95%CI 3.67‒22.30) and operation duration >240 min (OR=4.88, 95%CI 1.92‒12.42) were independent risk factors for blood loss >500 ml (P<0.05). Compared with patients with blood loss ≤500 ml, those with blood loss >500 ml showed remarkably extended activated coagulation time (ACT) (P<0.05). There was a correlation between abnormal r‑TEG and blood loss >500 ml (OR=3.56, 95%CI 1.38‒9.17, P<0.05). Patients with blood loss >500 ml presented increases in the incidences of delayed recovery, pulmonary infection and deep venous thrombosis, and hospitalization cost, compared with those with blood loss ≤500 ml (P<0.05). Conclusions Large tumor volume (with a diameter ≥4 cm), meningioma resection and operation duration >240 min are the risk factors of significant increases in intraoperative blood loss.