Objectives: This study intends to explore the effects of the surgery-first approach (SFA) on quality of life and mental health of patients who undergo orthognathic surgery compared to the conventional three-stage approach (CTA)., Data: The analysis included eight studies with a total of 307 patients, of which one was randomized controlled trial (RCT), one was clinical controlled trial (CCT), and six were non-randomized studies of interventions (NRSIs)., Sources: Electronic databases such as Medline, Embase, Scopus, and Web of Science were searched for eligible trials up to April 2023., Study Selection: RCTs, CCTs, and NRSIs, which compared the quality of life or mental health of orthognathic patients treated with SFA and CTA, were included in this study. The meta-analysis showed that the standardized mean differences (SMD) of Oral Health Impact Profiles-14 (OHIP-14) scores and the Orthognathic Quality of Life Questionnaire (OQLQ) between SFA and CTA were -1.58 (P = 0.05) and -2.99 (P < 0.00001) at the termination of the first-stage treatment, which altered to -0.94 (P = 0.54) and 0.09 (P = 0.65) after total treatment. Two studies applied the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) and the Beck Depression Inventory (BDI-II) to examine mental health, resulting in a trend similar to the former scales., Conclusion: In contrast to the conventional procedure, orthognathic treatment with SFA can instantly enhance the quality of life at the end of the first-stage treatment but has similar effects after the overall treatment. Moreover, SFA has a positive impact on psychological conditions., Clinical Significance: This study first systematically reviewed the effect of SFA on patients' mental well-being. According to our findings, it is better to select SFA if possible. Otherwise, the patient's psychological condition should be monitored appropriately throughout decompensation for better well-being both physically and mentally., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)