Objective This study sought to evaluate the impact of health care strike action on patient mortality. Data Sources EMBASE, PubMed CINAHL, BIOETHICSLINE, EconLit, WEB OF SCIENCE, and grey literature were searched up to December 2021. Study Design A systematic review and meta-analysis were utilized. Data Collection/Extraction Random-effects meta-analysis was used to compare mortality rate during strike versus pre- or post-strike, with meta-regression employed to identify factors that might influence the potential impact of strike action. Studies were included if they were observational studies that examined in-hospital/clinic or population mortality during a strike period compared with a control period where there was no strike action. Principal Findings Seventeen studies examined mortality: 14 examined in-hospital mortality and three examined population mortality. In-hospital studies represented 768,918 admissions and 7191 deaths during strike action and 1,034,437 admissions and 12,676 deaths during control periods. The pooled relative risk (RR) of in-hospital mortality did not significantly differ during strike action versus non-strike periods (RR = 0.91, 95% confidence interval 0.63, 1.31, p = 0.598). Meta-regression also showed that mortality RR was not significantly impacted by country (p = 0.98), profession on strike (p = 0.32 for multiple professions, p = 0.80 for nurses), the duration of the strike (p = 0.26), or whether multiple facilities were on strike (p = 0.55). Only three studies that examined population mortality met the inclusion criteria; therefore, further analysis was not conducted. However, it is noteworthy that none of these studies reported a significant increase in population mortality attributable to strike action. Conclusions Based on the data available, this review did not find any evidence that strike action has any significant impact on in-hospital patient mortality.