We conducted a meta-analysis to assess the outcome of prolonged postoperative antibiotics (PA) on wound healing in orthognathic surgery (OS). A systematic literature search up to January 2023 was performed and 1021 related studies were evaluated. The chosen studies comprised 1057 OS subjects who participated in the selected studies’ baseline, 446 of them used short-term PA, and 611 used long-term PA. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of prolonged PA on wound infection after OS by the dichotomous methods with a random or fixed effect model. The short-term PA resulted in significantly higher wound infection (OR, 4.27; 95% CI, 2.97-6.14, P < 0.001) with low heterogeneity (I = 27%) compared to the long-term PA in OS. The short-term PA resulted in significantly higher wound infection compared to the long-term PA in OS. Though care should be taken when dealing with the results since a large number of the selected studies had <100 subjects as a sample size.