Two hundred forty-five patients with OTA type 42 and 43A tibial fractures were randomized to receive suprapatellar nailing (n=128) or infrapatellar nailing (n=117). The primary outcome of interest was knee pain, assessed using the Visual Analog Scale (VAS) after kneeling. Secondary outcomes of interest included the Aberdeen Kneeling Test (AKT), Aberdeen Standing Test (AST), Lysholm score, Photographic Knee Pain Map (PKPM), EQ-5D, knee range of motion (ROM), Work Productivity and Activity Impairment Questionnaire (WPAI), fracture reduction, tibial alignment, and union rates. Outcomes were assessed at 6, 16, 26, and 52 weeks post-operatively. Overall, the results of the study revealed that suprapatellar nailing led to significantly lower VAS kneeling scores and better weight-bearing capacity in the operative knee at all time points. Additionally, suprapatellar nailing showed a significantly higher rate of anatomic fracture reduction. These findings suggest that suprapatellar nailing may be more effective in reducing post-operative knee pain and improving fracture reduction compared to infrapatellar nailing.