Purpose Bleeding volume in orthognathic surgery (OS) varies considerably, although OS comprises standardized procedures and the patient population consists of young healthy individuals. The aim of this prospective cohort study was to investigate the influence of preoperative sex-related differences in hemostatic parameters on intraoperative bleeding (IOB) volume in OS. Materials and Methods Patients scheduled for routine OS in our department in Esbjerg, Denmark, were included as study patients in this short-term cohort study. The primary predictor variable was patient sex, and the primary outcome variable was IOB volume measured in milliliters. Secondary outcome variables included preoperative measures of hematologic variables, thromboelastography, fibrinogen concentration, D-dimer concentration, prothrombin fragment 1+2 (F1+2) concentration, and type of osteotomy. Data analyses included the χ 2 test, Mann-Whitney U test, Pearson product moment correlation analysis, and analysis of covariance for analyses of dichotomous variables, comparison between sex, correlations between IOB volume and secondary predictors, and adjustment for confounders, respectively. Results Forty-one consecutive patients undergoing bimaxillary OS were included and subsequently grouped according to sex (26 men and 15 women). The main finding was that male patients bled twice as much as female patients on average (400 mL [interquartile range, 300 to 500 mL] vs 200 mL [interquartile range, 63 to 288 mL]; P = .001). Age and preoperative measures of thromboelastography, fibrinogen concentration, D-dimer concentration, and F1+2 concentration were significantly associated with sex (P = .001, P = .002, P = .007, and P = .014, respectively). The significant association between sex and IOB volume disappeared when adjusted for these confounders (P = .18). Conclusions Preoperative sex-related increases in measures of fibrin turnover predict IOB volume in bimaxillary OS, with women displaying a significantly lower IOB volume than men.