Objectives: Novel methods for preserving primary teeth can help to maintain their developmental, esthetic, and functional capabilities. The aim of this study was to assess the success of the repair of bony defects, caused by pre-treatment perforations, with a mixture of three antibiotics combined with simvastatin (3Mixtatin) compared to MTA in hopeless primary molars. Study design: In this randomized clinical trial, 80 teeth from 65 healthy children aged 3-6 years with interradicular or periapical root resorption and/or perforation in primary molars were treated either with 3Mixtatin or MTA before conventional pulpectomy and restoration. The subjects were followed up clinically and radiographically for 4, 6, 12 and 24 months after pulp treatment to evaluate and compare the healing process. The data were compared using chi-square test at a significance level of 0.05. Results: By the end of 24 months in 3Mixtatin group, 31 (96.8%) teeth revealed no clinical signs or symptoms with arrested resorption progress in radiographs. In MTA group, clinical signs and symptoms including pain, mobility and sinus tract were observed in 18 (48.6%) teeth with cessation of root/interradicular radiolucency in 7 (18.9%) teeth without bone repair. Conclusions: Radiographic and clinical healing occurred more successfully following 3Mixtatin treatment compared to treatment with MTA, it may lead to a paradigm shift in the pulpal treatment of primary teeth in the future.