Abstract: [Objective] To analyze the safety and effectiveness of 3D printing personalized guide assisted screw fixation in the treatment of Sanders type II and III calcaneal fractures. [Methods] 78 patients with Sanders type II and III calcaneal fractures in our hospital were retrospectively analyzed. Patients in 3D group received 3D printing personalized guide assisted screw fixation (39 cases); patients in traditional group received traditional operation (39 cases). The observation indexes included perioperative conditions, follow-up indexes and imaging evaluation. [Results] The perioperative indexes of patients in 3D group were significantly lower than those in traditional group (P < 0.05); the incidence of adverse reactions in 3D group was significantly lower than that in traditional group (P < 0.05). The scores of ankle pain and function in 3D group were significantly better than those in traditional group (P < 0.05). The imaging indexes such as Bohler angle and Gissane angle in 3D group were significantly better than those in traditional group (P < 0.05). [Conclusion] In the treatment of Sanders type II and III calcaneal fractures, 3D printing personalized guide assisted screw internal fixation has satisfactory effect in restoring ankle function, relieving pain symptoms and promoting fracture healing; it can also effectively avoid the occurrence of postoperative adverse events, and has good treatment safety and effectiveness.