Aim and Background: This meta-analysis aimed to study the failure rate and related risk factors associated with the use of orthodontic mini-screws in anchorage reinforcement. Method and Materials: This meta-analysis was started with a search for keywords ‘mini-screw’, ‘micro-screw’, ‘mini-implant’ and ‘failure rate’ in the databases of several search engines, including Google Scholar, PubMed, Science Direct and Scopus. Articles were selected based on inclusion criteria (e.g. clinical trials, retrospective, and human studies) and exclusion criteria (e.g. on-plant, palatal and conventional implants). The quality of selected studies for this study was assessed by the PRISMA checklist. The mean and standard deviation of failure rates were determined. The random-effect model was used to evaluate the effect of each risk factor on the failure rate. This study aimed to calculate the failure rate, and identify the risk factors involved in the failure rate of using mini-screws by meta-analysis. Results: A total of 20 out of 1,995 studies were selected up to 2016, to assess the overall failure rate of mini-screw, and to investigate the associated risk factors. Of 4,826 mini-screw implants used in 2,327 patients, the overall failure rate was 15.08% (95% CI). The statistical significance was set at P<0.01. Failures of mini-screw were not associated with the mini-screw insertion site (right or left), growth pattern, Gender, type of malocclusion and mini-screw length. They were significantly associated with the jaw insertion, age, and type of gingiva (attached or movable) (P<0.006). Conclusion: The overall mean of the failure rate in this study was 15.08 %. Related risk factors such as jaw insertion, age, and type of gingiva affected the failure rate. Collectively, the results of this study indicate that mini-screws with low failure rates are the best alternative for anchorage reinforcement.