Background: A high incidence (40–73%) of postoperative nausea and vomiting (PONV) has been reported following orthognathic surgery, and various risk factors have been associated with it. Identifying PONV risk factors based on initial onset time will help establish preventive measures. This study aimed to identify factors that are significantly related to PONV based on the initial onset time after orthognathic surgery. Methods: This study included 590 patients who underwent orthognathic surgery. Multivariate logistic regression analysis was performed to identify the risk factors that are significantly related to PONV. The objective variables were classified into three categories: no PONV, early PONV (initial onset time: 0–2 h after anesthesia), and late PONV (initial onset time: 2–24 h after anesthesia). The explanatory variables included relevant risk factors for PONV, as considered in previous studies. Results: Total intravenous anesthesia with propofol was a significant depressant factor for early PONV (adjusted odds ratio [aOR] = 0.340, 95% confidence interval [CI] = 0.209–0.555) and late PONV (aOR = 0.535, 95% CI = 0.352–0.814). The administration of a combination of intraoperative antiemetics (vs. no administration) significantly reduced the risk of early PONV (aOR = 0.464, 95% CI = 0.230–0.961). Female sex and young age were significant risk factors for late PONV (aOR = 1.492, 95% CI = 1.170–1.925 and unit aOR = 1.033, 95% CI = 1.010–1.057, respectively). Conclusion We identified factors that are significantly related to PONV based on the initial onset time after orthognathic surgery. Total intravenous anesthesia with propofol significantly reduced the risk of PONV not only in the early period (0–2 h after anesthesia) but also in the late period (2–24 h after anesthesia).