Intraoperative handoffs between anesthesia clinicians are critical for care continuity. However, such handoffs pose a significant threat to patient safety. This systematic review synthesizes the empirical evidence on the (a) effect of intraoperative handoffs on outcomes and (b) effect of intraoperative handoff tools on outcomes. All studies on intraoperative handoffs and handoff tools published until September 2019, in any study setting and population, and with no prespecified criteria on the type of comparison and outcome were included. Data extracted from the included studies were aggregated to identify common patterns related to the type of surgery, clinician(s) involved, patient population, handoff tool, the tool design approach (where relevant), tool implementation strategies, and finally, all reported clinical and process outcomes. Quality of studies was assessed using the Newcastle-Ottawa Scale (NOS). Fourteen studies met the inclusion criteria. All included studies used adult patients. Eight studies were retrospective cohort studies that used administrative or electronic health record (EHR)–based databases to investigate the effects of intraoperative handoffs on morbidity and mortality. These studies included a total of 680,855 surgeries, with 139,426 of these surgeries having at least 1 handoff (20.47%). Seven of the studies found a positive association between intraoperative handoffs and considered outcomes. However, a pooled meta-analysis across these studies was not feasible across the retrospective studies due to differing surgical populations and varying definitions of the considered outcomes. Six studies used a nonrandomized prospective design to evaluate the effects of handoff tools on process-based outcomes such as clinician satisfaction, information transfer, handoff duration, and adherence. Five of the 6 handoff tools were checklist based. All prospective tool-based studies relied on small samples and reported a significant improvement on the considered process-based outcomes. The median quality score among retrospective (median [interquartile range {IQR}] = 9 [1]) was significantly higher than that of prospective (median [IQR] = 5 [1.5]) studies (U = 21, P = .0017). This systematic review provides a unique appraisal of the current state of intraoperative handoff research. To improve the quality and outcomes of handoffs, future efforts should focus on design and implementation of standardized handoff tools integrated within EHR systems, consider the use of similar metrics for evaluating handoff process and clinical outcomes, and improve the execution and reporting of studies using standard protocols and guidelines.