PurposeTargeted temperature management (TTM) may improve survival and functional outcome in comatose survivors of out-of-hospital cardiac arrest (OHCA), though the optimal target temperature remains unknown. We conducted a systematic review and network meta-analysis to investigate the efficacy and safety of deep hypothermia (31–32 °C), moderate hypothermia (33–34 °C), mild hypothermia (35–36 °C), and normothermia (37–37.8 °C) during TTM.MethodsWe searched six databases from inception to June 2021 for randomized controlled trials (RCTs) evaluating TTM in comatose OHCA survivors. Two reviewers performed screening, full text review, and extraction independently. The primary outcome of interest was survival with good functional outcome. We used GRADE to rate our certainty in estimates.ResultsWe included 10 RCTs (4218 patients). Compared with normothermia, deep hypothermia (odds ratio [OR] 1.30, 95% confidence interval [CI] 0.73–2.30), moderate hypothermia (OR 1.34, 95% CI 0.92–1.94) and mild hypothermia (OR 1.44, 95% CI 0.74–2.80) may have no effect on survival with good functional outcome (all low certainty). Deep hypothermia may not improve survival with good functional outcome, as compared to moderate hypothermia (OR 0.97, 95% CI 0.61–1.54, low certainty). Moderate hypothermia (OR 1.23, 95% CI 0.86–1.77) and deep hypothermia (OR 1.27, 95% CI 0.70–2.32) may have no effect on survival, as compared to normothermia. Finally, incidence of arrhythmia was higher with moderate hypothermia (OR 1.45, 95% CI 1.08–1.94) and deep hypothermia (OR 3.58, 95% CI 1.77–7.26), compared to normothermia (both high certainty).ConclusionsMild, moderate, or deep hypothermia may not improve survival or functional outcome after OHCA, as compared to normothermia. Moderate and deep hypothermia were associated with higher incidence of arrhythmia. Routine use of moderate or deep hypothermia in comatose survivors of OHCA may potentially be associated with more harm than benefit.