AIM: To evaluate the postoperative analgesic efficacy and safety of ketorolac tromethamine in tibial plateau fracture (TPF) patients undergoing open reduction and internal fixation (ORIF) surgery. METHODS: This retrospective cohort study included 194 TPF patients treated at Dongtai People's Hospital between October 2022 and March 2024. Patients meeting the inclusion criteria were divided into two groups: the ketorolac tromethamine group (n = 104), who received ketorolac tromethamine combined with imrecoxib, and the control group (n = 90), who received imrecoxib alone after ORIF. Baseline characteristics, postoperative analgesia (measured using the visual analogue scale (VAS) and Ramsay sedation scores), fracture healing parameters (healing time, alkaline phosphatase (ALP), bone gamma-carboxyglutamate protein (BGP), and collagen type I carboxy-terminal propeptide (PICP), and adverse events were evaluated preoperatively and at hospital discharge. RESULTS: The ketorolac tromethamine group demonstrated significantly lower VAS scores (1 h, p = 0.017; 6 h, p = 0.022) and Ramsay sedation scores (1 h, p = 0.017; 6 h, p = 0.034) after anesthesia recovery compared to the control group. No significant differences between the two groups were observed in fracture healing time, ALP, BGP, or PICP levels (p > 0.05). The incidence of adverse events was comparable between the groups (p > 0.05). Laboratory results, including routine blood tests (neutrophil-to-lymphocyte ratio, p = 0.080; hemoglobin, p = 0.830), liver function tests (alanine aminotransferase (ALT), p = 0.773; aspartate aminotransferase (AST), p = 0.629), and renal function markers (creatinine, p = 0.596; uric acid (UA), p = 0.466; β2-microglobulin, p = 0.605), exhibited no significant differences between the two groups. CONCLUSIONS: The combination of ketorolac tromethamine and imrecoxib was more effective than imrecoxib alone in alleviating postoperative pain in TPF patients undergoing ORIF. Ketorolac tromethamine had no significant impact on bone healing, indicating its potential as bone-safe analgesia when combined with imrecoxib.