OBJECTIVES: This study aims to compare non-compression and compression intramedullary nailing in an experimental femoral shaft osteotomy model in terms of radiological, histological, and biomechanical aspects. MATERIALS AND METHODS: Twenty-four white New Zealand rabbits (average weight 4.3 kg; range 4 to 4.8 kg) were divided into three groups. A right femoral osteotomy was performed in all rabbits and all femurs were fixed with titanium compression interlocking intramedullary nail. After locking of nails, no compression was performed in group 1 while 0.5 mm and 1 mm compressions were performed in group 2 and 3, respectively. All rabbits were sacrificed four weeks after operation. Fracture sites were examined histologically and radiologically. Finite element analyses were performed. RESULTS: Radiological scores of groups 2 and 3 were significantly higher than group 1. There was no significant difference between groups 2 and 3 radiologically. Best histological scores were achieved in group 2. According to finite element analyses, osteotomy site in group 2 was exposed to 1240 N of load and 34.5 MPa of mean stress. CONCLUSION: Compression interlocking intramedullary nailing provides faster fracture healing than non-compression interlocking intramedullary nailing. Best histological fracture healing scores were obtained with 0.5 mm compression performed at the fracture site.