BACKGROUND Intramedullary nailing (IMN) is currently considered the gold standard in the surgical treatment of tibial shaft fractures in adult patients. In this case-control comparative study, we aimed to compare the efficacy of minimally invasive plate osteosynthesis (MIPO) and IMN in treating tibial shaft fractures. METHODS The clinical and radiological outcomes, such as a modified trauma scale, operation time, fracture healing, rate of re-operation, and complications such as malunion, nonunion, shortening, and infection were assessed between IMN and MIPO for the treatment of tibial shaft fractures. RESULTS Seventy-three skeletally mature patients who underwent IMN (group I) or MIPO (group M) for a closed extra-articular tibial shaft fracture (AO/OTA type 42) from June 2010 to May 2016 were retrospectively reviewed. The mean age was 51.16 (18~79) years, and the mean follow-up period was 22 (12~50) months. Bony union was achieved in all cases but one for each group - group I (35 cases) and group M (36 cases) (p > 0.05). Mean callus formation was observed in 12 (8 - 16) weeks in both groups (p > 0.05). There was no significant difference in operative time, hospital stay, bone healing, and the rate of complications among the two groups (p > 0.05). There was also no postoperative difference in functional evaluation between the two methods (p > 0.05). CONCLUSIONS No discrepancy was found in radiological and clinical outcomes between IMN and MIPO for tibial shaft fractures. It can be concluded that both IMN and MIPO are equally effective treatment modalities for tibial shaft fractures.