Botulinum toxin (BTX) is considered an efficient and safe therapy for postoperative scars that improves visual and functional quality. However, the optimal timing for injection remains under debate due to conflicting evidence. The aim of this study is to evaluate the efficacy and safety of BTX applied immediately after wound closure in the quality assessment of postoperative scars. This is a systematic review and meta-analysis following the PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) 2020 guidelines. Searches were performed in PubMed, EMBASE, Web of Science, and Cochrane until September 10, 2024, including randomized or prospective studies on BTX applied immediately after wound closure, with exclusions for keloids or hypertrophic scars treatment studies, non-English studies, reviews, case reports, letters, and abstracts. The quality of scars was assessed using appropriate and widely validated tests and scales when at least 3 studies selected in the meta-analysis utilized them. The mean difference (MD) was used to explore the difference among different groups. Nine randomized trials and 1 prospective study in a total of 521 were identified in this meta-analysis. BTX showed no significant difference in Vancouver Scar Scale score (MD = -0.35, 95% confidence interval [CI] = -1.01 to 0.30, P = 0.29) compared with control, higher visual analog scale score (MD = 1.29, 95% CI = 0.68 to 1.90, P < 0.01), and reduced scar width (MD = -0.19, 95% CI = -0.30 to -0.09, P < 0.01). No adverse events were found in the included studies. This meta-analysis demonstrated that BTX injections immediately after wound closure are safe and improve scars quality. BTX time of injection requires further studies to provide better clinical applications.