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The purpose of this systematic review and meta-analysis was to assess the efficacy of methylprednisolone compared to other drugs to control postoperative complications following third molar surgery. PubMed and Google Scholar were used for article searching. Thereafter, the trials meeting the selection criteria and with high methodological quality, according to the Cochrane Collaboration’s risk of bias tool, were included in this study. The inverse variance test and mean difference using the Review Manager Software 5.3 for Windows were used to carry out data analysis. Qualitative analysis shows that methylprednisolone is more effective than NSAIDs, but inferior to dexamethasone, for controlling postoperative complications after third molar removal. The quantitative analysis showed no statistical difference for pain control, while trismus evaluation showed a statistical difference after 7 postoperative days in favor of methylprednisolone, when compared to other drugs. In conclusion, methylprednisolone was more effective for trismus control compared to other drugs after lower third molar surgery.