Aim: To investigate the outcome of autologous bone marrow mesenchymal stem cells (BMMSCs) and platelet-rich plasma in combination with calcium phosphate cement (CPC) scaffold to reconstruct femoral critical bone defects in mini-pigs. Materials & methods: Scanning electron microscopy, micro-computed tomography evaluation and quantitative histological assessment were used. Results & conclusion: BMMSCs were attached to the CPC scaffold after 7 days of culture and decreased the residual CPC material in each group at 12 weeks compared with 6 weeks. The newly formed bone area was higher in the CPC+SC+P group than in the CPC group at each time point (all p < 0.05). The strategy of CPC combined with BMMSCs and platelet-rich plasma might be an effective method to repair bone defects.