The objective of this study was to conduct a systematic review and meta-analysis to evaluate the existing information on the efficacy of commercial vaccination to reduce the prevalence of Escherichia coli O157:H7 in weaned cattle in beef feedlot finishing systems under commercial conditions. Currently, only two commercial vaccines exist, and thus, only publications reporting the use of vaccines targeting type III secreted proteins and/or siderophore receptor and porin proteins (SRP) were considered relevant. A total of 18 studies reporting 45 comparisons were included in this review. Meta-analyses were conducted variously on (i) pre-harvest outcomes, (ii) at-harvest outcomes and (iii) both pre-harvest and at-harvest outcomes combined. Overall, efficacy of vaccination was consistently observed. Efficacy and homogeneity of the results was demonstrated for the two-dose regimen, allowing us to conclude with confidence that the two-dose approach is efficacious. For pre-harvest outcomes and two-dose regimens, the odds ratios (OR) were 0.53 (95% CI = 0.45–0.62) for the two vaccines combined and 0.49 (95% CI = 0.40–0.60) for vaccine targeting type III secreted proteins. The test for heterogeneity among studies yielded a Q test P = 0.354 for the two vaccines combined and Q test P = 0.269 for the vaccine targeting type III secreted proteins, indicating homogeneity in both cases. For pre- and at-harvest outcomes combined and two-dose regimens, the odds ratios (OR) were 0.52 (95% CI = 0.44–0.61) for the two vaccines combined and 0.45 (95% CI = 0.34–0.60) for vaccine targeting type III secreted proteins. The test for heterogeneity among studies yielded a Q test P = 0.134 for the two vaccines combined indicating homogeneity and Q test P = 0.089 for the vaccine targeting type III secreted proteins indicating heterogeneity. Based on this meta-analysis, bovine vaccination appears to be an effective approach to the pre-harvest control of E. coli O157:H7.