Background: The infrapatellar branch of the saphenous nerve (IPBSN) is a purely sensory nerve innervating the anteromedial aspect of the knee and anteroinferior knee joint capsule. Total knee arthroplasty (TKA) is commonly used to treat end-stage arthritis, but the IPBSN is often injured and results in numbness around the anteromedial knee. The aim of this cadaveric study was to describe the course and variability of the IPBSN and to assess whether it is possible to preserve during a standard midline surgical approach in TKA. Methods: Ten fresh-frozen cadaver legs were dissected using a midline approach to the knee. Skin and subcutaneous flap were reflected to expose both the saphenous nerve and its branches. The branches of the IPBSN were identified, and their vertical distances above the tibial tuberosity (TB) were recorded: TB to inferior branch, to middle branch, and to superior branch. Results: There were 10 left-sided specimens (6 female, 4 male) with a mean age of 79.9 ± 9.8 years. 8 (80%) specimens had 2 branches of IPBSN while 2 (20%) specimens had 3 branches. The average distance from TB to the inferior branch was 16.8 ± 8.3 mm (3.0–28.0); middle branch, 24.0 ± 1.4 mm (23.0–24.9); and superior, 45.9 ± 7.7 mm (32.0–54.5). Conclusion: Our cadaveric study found no consistent way to preserve the IPBSN using a standard midline approach in TKA. It is important to provide proper patient education on this complication, and surgeons should be aware of approximate locations and variations of IPBSN while performing other knee procedures.