Bracket failure increases the treatment time of orthodontic therapy and burdens patients with unnecessary costs, increased chair time, and possible new appointments. To compare the bond failures of different orthodontic materials based on the results of available clinical studies. A systematic search of clinical trials was performed in the Cochrane, Embase, and Pubmed databases with no limitations. The list of investigated techniques contained conventional acid-etch primer (CM-AEP), self-etch primer (SEP), self-cure resin (SCR), and simple or resin-modified glass ionomer (RM-GIC) materials and procedures. Clinical studies reporting the failure rate of bonded brackets after using direct adhesive techniques on buccal sites of healthy teeth were included. Bracket failure rates from eligible studies were extracted by two authors independently. Risk ratios (RRs) were pooled using the random-effects model with DerSimonian-Laird estimation. Thirty-four publications, involving 1221 patients, were included. Our meta-analysis revealed no significant difference in the risk of bracket failures between SEP and CM-AEP. After 6, 12, and 18 months of bonding, the values of RR were 1.04 [95% confidence interval (CI), 0.67-1.61], 1.37 (95% CI, 0.98-1.92), and 0.93 (95% CI, 0.72-1.20), respectively. At 18 months, bracket failure was 4.9 and 5.2% for SEP and CM-AEP, respectively. Heterogeneity was good or moderate (I2 < 42.2%). The results of RM-GIC at 12 months indicated a 57% lower risk of bracket failure using SCR as compared with RM-GIC (RR: 0.38; 95% CI, 0.24-0.61). At 18 months, bracket failures for SCR and RM-GIC were 15.8 and 36.6%, respectively (RR: 0.44; 95% CI, 0.37-0.52, I2 = 78.9%), demonstrating three to six times higher failure rate than in the case of etching primer applications. A major limitation of the present work is that the included clinical trials, with no exceptions, showed variable levels of risk of bias. Another possible problem affecting the outcome is the difference between the clustering effects of the split mouth and the parallel group bracket allocation methods. The results revealed no significant difference between SEP and CM-AEP up to 18 months after application. RM-GIC had much worse failure rates than acid-etching methods; additionally, the superiority of SCR over RM-GIC was evident, indicating strong clinical relevance. Prospero with CRD42020163362.