The benefit of blood cardioplegia (BCP) compared to crystalloid cardioplegia (CCP) is still debatable. Our aim was to systematically review and synthesize all available evidence on the use of BCP and CCP to assess if any modality provides superior outcomes in pediatric cardiac surgery. A systematic literature search of the PubMed and Cochrane databases was performed with respect to the PRISMA statement (end-of-search date: January 30th, 2017). We extracted data on study design, demographics, cardioplegia regimens, and perioperative outcomes as well as relevant biochemical markers, namely cardiac troponin I (cTnI), lactate, and ATP levels at baseline, after reperfusion and postoperatively at 1, 4, 12, and 24 h as applicable. Data were appropriately pooled using random and mixed effects models. Our systematic review includes 56 studies reporting on a total of 7711 pediatric patients. A meta-analysis of the 10 eligible studies directly comparing BCP (n = 416) to CCP (n = 281) was also performed. There was no significant difference between the two groups with regard to cTnI and Lac at any measured time point, ATP levels after reperfusion, length of intensive care unit stay (WMD: −0.08, 95% CI −1.52 to 1.36), length of hospital stay (WMD: 0.13, 95% CI −0.85 to 1.12), and 30-day mortality (OR 1.11, 95% CI 0.43–2.88). Only cTnI levels at 4 h postoperatively were significantly lower with BCP (WMD: −1.62, 95% CI −2.07 to −1.18). Based on the available data, neither cardioplegia modality seems to be superior in terms of clinical outcomes, ischemia severity, and overall functional recovery.