Objective: To compare the clinical efficacy, safety, and prognosis of full-threaded headless cannulated compression screws (HCCSs) and anatomical plates (APs) in the treatment of triplane fractures of the distal tibia. Methods: In this retrospective study, 74 patients with triplane fractures of the distal tibia treated in our hospital from April 2017 to March 2019 were selected as the research subjects. Among them, 38 patients receiving full-threaded HCCSs were assigned to the research group (RG), and the remaining 36 patients receiving APs were assigned to the control group (CG). The general indices, including operation, fracture healing, and ambulation times, efficacy, and complications were recorded and compared between the two groups. Visual analogue scale (VAS) was applied to assess pain, and a quality of life (QOL) survey was conducted at 6 months after surgery. Results: Compared with the CG, the operation time, fracture healing time, and ambulation time of the RG were significantly shortened (P<0.05). The proportion of patients with excellent and good outcomes and Mazur Scores in the RG were higher than those in the CG (P<0.05). The frequency of complications in the RG was lower than that in the CG (P<0.05). The preoperative VAS score did not exhibit significant differences between the two groups (P<0.05), but the scores in the RG at T1 and T2 were significantly lower than those in the CG (P<0.001). The QOL score in the RG (76.17 +/- 8.57) was also significantly higher than in the CG (7154 +/- 8.02)(P<0.05). Conclusion: Full-threaded HCCSs are more effective and safer than APs and can effectively improve the prognosis of patients with triplane fractures of the distal tibia.