OBJECTIVE Minimizing intraoperative blood loss during hysterectomy is crucial to lessen associated perioperative morbidity. The aim of this investigation is to conduct a systematic review and meta-analysis of all randomized controlled trials (RCTs) that compared vasopressin versus normal saline in controlling intraoperative blood loss during hysterectomy. DATA SOURCES We screened 5 major databases (PubMed, Scopus, Web of Science, Embase, and the Cochrane Central Register of Controlled Trials) from inception till July 18, 2021. We used the following query search in all databases: (vasopressin OR arginine vasopressin OR argipressin OR antidiuretic hormone) AND (hysterectomy) AND (saline OR placebo OR control OR no treatment) AND (randomized OR randomised OR randomly). There was no language restriction during database screening. METHODS OF STUDY SELECTION We considered all studies that met the following evidence-based criteria: (1) patients: individuals undergoing hysterectomy for any indication, (2) intervention: vasopressin, (3) comparator: normal saline, placebo, or no treatment, (4) outcomes: reliable extraction of any of our endpoints, and (5) study design: RCTs. We assessed risk of bias of included studies and pooled endpoints as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI). We performed statistical analysis using the Review Manager software, version 5.4.0. TABULATION, INTEGRATION, AND RESULTS Seven RCTs with an overall low risk of bias met the inclusion criteria. This meta-analysis included a total of 455 patients; 232 and 223 patients were allocated to vasopressin and control group, respectively. The majority of RCTs were vaginal hysterectomy (n = 5), few abdominal hysterectomy, (n = 2) and no laparoscopic hysterectomy. The mean estimated intraoperative blood loss was significantly lower in favor of the vasopressin group compared with the control group (n = 6 RCTs, MD = -119.85 mL, 95% CI [-177.55, -62.14], p