Introduction <p>Hemorrhage represents a significant complication during laparoscopic myomectomy, with transfusion requirements occurring in 5–40% of procedures. Vasopressin, a potent vasoconstrictor, has been employed for hemostasis in gynecologic surgery but evidence regarding its efficacy and safety for laparoscopic myomectomy has not been systematically synthesized. This systematic review and meta-analysis comprehensively evaluates vasopressin efficacy and safety for hemostasis during laparoscopic fibroid removal.</p> Evidence acquisition <p>Systematic search of PubMed/MEDLINE, EMBASE, Cochrane CENTRAL, Web of Science, and Scopus databases conducted until November 28, 2025, identified studies comparing vasopressin to control interventions during laparoscopic myomectomy. Randomized controlled trials and observational comparative studies reporting blood transfusion requirement, blood loss, or adverse events were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias using Cochrane RoB 2 and ROBINS-I tools. Random-effects meta-analysis calculated pooled odds ratios (OR) for transfusion and mean differences (MD) for blood loss. GRADE methodology assessed evidence certainty. Subgroup analyses evaluated effect modification by fibroid characteristics, study quality, and surgical approach.</p> Evidence synthesis <p>After removal of protocol-only, non-laparoscopic/open, hysteroscopic-only, and unverifiable records from the quantitative synthesis, eight verified comparative studies were retained for qualitative synthesis. Five studies contributed to the revised primary transfusion analysis, demonstrating lower transfusion requirement with vasopressin versus control (OR 0.18, 95% CI: 0.09–0.34, <i>P</i> &lt; 0.001; approximate NNT = 8). Sensitivity analysis excluding the high-risk observational study Thiek [<CitationRef CitationID="CR1">1</CitationRef>] showed a similar but attenuated effect (OR 0.21, 95% CI: 0.11–0.41). Six laparoscopic/robot-assisted datasets showed reduced intraoperative blood loss (MD -100.6 mL, 95% CI: -134.3 to -66.9; I²=38%). Cohen [<CitationRef CitationID="CR2">2</CitationRef>] was the only included study that incorporated surgeon-estimated blood loss; excluding this study yielded MD -109.2 mL (95% CI: -136.5 to -81.9; I²=0%). Blood-loss findings should therefore be interpreted as hypothesis-generating because ascertainment methods were not fully uniform across studies. Hemoglobin preservation was directionally consistent but should be interpreted with caution because of differences in study design and measurement timing. Reported adverse events were mainly transient hemodynamic changes, especially mild hypertension, with no permanent vasopressin-attributable cardiovascular injury documented in the verified evidence base.</p> Conclusions <p>Current evidence suggests that intramyometrial vasopressin may reduce transfusion requirement and estimated blood loss during laparoscopic or robot-assisted laparoscopic myomectomy when diluted preparations and careful hemodynamic monitoring are used. However, the certainty of the evidence is limited by small study numbers, observational data, publication-bias signals, and residual methodological heterogeneity. Vasopressin should therefore be considered a useful hemostatic adjunct in selected higher-risk cases rather than an unequivocal universal standard. Larger, prospectively registered randomized trials are needed to define optimal dosing, dilution, safety monitoring, and long-term reproductive outcomes.</p> Prospero registration <p>CRD420261340513; registered 14 March 2026 after completion of the literature search on 28 November 2025, and therefore retrospectively registered.</p>