BACKGROUND: The aim of this systematic review was to compare the effects of regional analgesic (RA) techniques with systemic analgesia on postoperative pain, nausea and vomiting, resources utilization, reoperation, death, and complications of the analgesic techniques in children undergoing cardiac surgery. METHODS: A search was done in May 2018 in PubMed, Embase, and the Cochrane Central Register of Controlled Trials for randomized controlled trials comparing RA techniques with systemic analgesia. Risks of bias of included trials were judged with the Cochrane tool. Data were analyzed with fixed- (I < 25%) or random-effects models (I >/= 25%). The quality of evidence was graded according to the Grading of Recommendations Assessment, Development, and Evaluation working group scale. RESULTS: We included 14 randomized controlled trials with 605 participants (312 to RA and 293 to the comparator). RA reduces pain up to 24 hours after surgery. At 6-8 hours after surgery, the standardized mean difference was -0.81 (95% confidence interval [CI], -1.22 to -0.40; low-quality evidence). We did not find a difference for nausea and vomiting (risk ratio [RR], 0.89; 95% CI, 0.61-1.31; very low-quality evidence), duration of tracheal intubation (standardized mean difference, -0.18; 95% CI, -0.40 to 0.05; low-quality evidence), intensive care unit length of stay (mean difference, -0.10 hours; 95% CI, -1.31 to 1.12 hours; low-quality evidence), hospital length of stay (mean difference, -0.02 days; 95% CI, -1.16 to 1.12 days; low-quality evidence), reoperation (RR, 0.76; 95% CI, 0.17-3.28; low-quality evidence), death (RR, 0.50; 95% CI, 0.05-4.94; low-quality evidence), and respiratory depression (RR, 2.06; 95% CI, 0.20-21.68; very low-quality evidence). No trial reported signs of local anesthetic toxicity or lasting neurological or infectious complications related to the RA techniques. One trial reported 1 transient ipsilateral episode of diaphragmatic paralysis with intrapleural analgesia that resolved with cessation of local anesthetic administration. CONCLUSIONS: Compared to systemic analgesia, RA techniques reduce postoperative pain up to 24 hours in children undergoing cardiac surgery. Currently, there is no evidence that RA for pediatric cardiac surgery has any impact on major morbidity and mortality. These results should be interpreted cautiously because they represent a meta-analysis of small and heterogeneous studies. Further studies are needed.