Objective: Meta-analysis to evaluate complications in the use of autogenous bone and bone substitutes and to compare bone substitutes, specifically HA, polyetheretherketone (PEEK) and titanium materials. Methods: Search of PubMed, Cochrane, Embase and Google scholar to identify all citations from 2010 to 2019 reporting complications regarding materials used in cranioplasty. Results: 20 of 2266 articles met the inclusion criteria, including a total of 2913 patients. The odds of overall complication were significantly higher in the autogenous bone group (n = 214/644 procedures, 33.2%) than the bone substitute groups (n = 116/436 procedures, 26.7%, CI 1.29-2.35, p < 0.05). In bone substitutes groups, there was no significant difference in overall complication rate between HA and Ti (OR, 1.2; 95% CI, 0.47-3.14, p = 0.69). PEEK has lower overall complication rates (OR, 0.51; 95% CI, 0.30-0.87, p = 0.01) and lower implant exposure rates (OR, 0.17; 95% CI, 0.06-0.53, p = 0.002) than Ti, but there was no significant difference in infection rates and postoperative hematoma rates. Conclusions: Cranioplasty is associated with high overall complication rates with the use of autologous bone grafts compared with bone substitutes. PEEK has a relatively low overall complication rates in substitutes groups, but still high infection rates and postoperative hematoma rates. Thus, autologous bone grafts should only be used selectively, and prospective long-term studies are needed to further refine a better material in cranioplasty.