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Objective To investigate the therapeutic effect of 3D printed anatomical tibial prosthesis in the repair of bone defects after debridement of tibial osteomyelitis. Methods Five patients with bone defects after debridement of lower tibial osteomyelitis were treated between January 2015 and December 2020 in the Eighth Medical Center of Chinese PLA General Hospital. Their bone defects were repaired via 3D printed anatomical titanium alloy tibial prosthesis. The duration of surgery and volume of intraoperative bleeding were recorded. The patients were followed up regularly for 12 months. Visual analog scale (VAS) score, Hospital for Special Surgery (HSS) knee score, American Orthopedic Foot and Ankle Score (AOFAS) Ankle Hindfoot Scale and 6-minute walk distance (6MWD), Timed "Up and Go" (TUG) test and 36-Item Short Form Health Survey were used to assess the clinical efficacy. The wound healing and complications were observed, while leukocyte count, C-reactive protein level and erythrocyte sedimentation rate (ESR) were detected and calculated. Results The mean duration of operation was 156.75±32.40 min, while the mean amount of intraoperative bleeding was 490.00±84.06 mL. After 12 months of follow-up, the VAS pain score, HSS score and AOFAS score were significantly improved (P < 0.05). The time for TUG and 6MWD were significantly extended and lengthened after operation (P < 0.05). The scores of postoperative qualities of life were elevated (P < 0.05). During the 12-month follow-up, the leukocyte count, ESR and C-reactive protein level were all within the normal ranges. The wounds healed well without sinus formation. Conclusion 3D printed anatomical titanium alloy tibial prosthesis has the advantages of effectively restoring good function of the lower limbs, mitigating preoperative pain and reducing postoperative complications.