Purpose: The aim of the study was to compare the clinical efficacy of methylprednisolone with ibuprofen to ibuprofen alone on the postoperative sequelae of surgical removal of impacted third molars. Materials and Methods: The present study was conducted on the 35 patients requiring surgical extraction of bilateral impacted third molars attending the Outpatient Department of Oral and Maxillofacial Surgery, Guru Nanak Dev Dental College and Research Institute. The impacted teeth were removed in two sessions at least 3 weeks apart. The selected patients were randomly put on regimen 1 or regimen II at either the first or second surgery in accordance with randomization plan. The measurements and recordings for pain, swelling, and interincisal distance (mouth opening), were made on 1 st , 3 rd , and 7 th day postoperatively on the scales designed for the purpose. The data recorded was compiled and put to statistical analysis. Results: It was observed from the present study that postoperative sequelae, that is, pain, swelling, and trismus was significantly less in the regimen I group than regimen II group on the 1 st and 3 rd postoperative day. Conclusion: The results of this study substantiate the fact that a single class of drugs (nonsteroidal anti-inflammatory drug (NSAID)) is less effective in controlling postoperative inflammatory sequelae than the combination of ibuprofen (NSAID) and methylprednisolone (corticosteroid) following the third molar surgery. Therefore, this pharmaceutical combination should be considered for attenuation of postoperative sequelae in healthy patients undergoing surgical removal of impacted mandibular third molar.