Objective: To investigate the effect of seamless optimized nursing mode on rehabilitation of patients with tibiofibular fracture after operation. Methods: From January 2020 to August 2021, 100 patients with tibiofibular fractures in Suzhou Municipal Hospital were selected as the subjects. They were divided into a control group (n=50) and an observation group (n=50) according to the random number table method. The control group adopted the routine nursing mode during orthopedic perioperative period, and the observation group adopted the seamless optimized nursing mode based on the control group. The related indicators of rehabilitation process, changes in the psychological state [Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS)], pain [Visual Analogue Scale (VAS)], knee joint function (Lysholm knee score scale), and activities of daily living (Barthel index scale) were compared between the 2 groups before and after the intervention. Results: The first ambulation time and hospitalization time of the observation group were shorter than those of the control group (both P<0.05),  the hospitalization expense of the observation group was less than those of the control group (P<0.05), and the nursing satisfaction of the observation group was higher than that of the control group (P<0.05). At discharge, the SAS and SDS scores of the observation group were significantly lower than those of the control group (both P<0.05). At 1, 3, and 7 days after the operation, the VAS scores of the observation group were significantly lower than those of the control group (all P<0.05). After 3 and 6 months of intervention, Lysholm knee score and Barthel index score in the observation group were significantly higher than those in the control group (both P<0.05). Conclusion: Seamless optimized nursing can effectively relieve postoperative pain, improve patients’ bad mood, promote postoperative rehabilitation, and improve postoperative knee joint function and activities of daily living in patients with tibiofibular fracture.