Purpose <p>The infrapatellar branch of the saphenous nerve (IPBSN) plays a critical role in cutaneous innervation of the anterior knee and is frequently implicated in both acute and chronic post-surgical pain. Due to its anatomical variability, precise localization is essential for effective nerve blocks and minimizing iatrogenic injury. This study evaluates the feasibility of two distal ultrasound-guided approaches for selective IPBSN blocks, with the aim of addressing the limitations of proximal techniques.</p> Methods <p>Anatomical layer-by-layer dissections of two paired lower limbs and transverse cross-sections of a third limb were used to map the IPBSN’s course and its relationship to the sartorius muscle. Based on these findings, two distal ultrasound-guided approaches were tested: a proximal medial para-patellar approach at the level of the patella’s superior aspect and a distal medial para-patellar approach near the medial femoral condyle. Ultrasound-guided injections (0.1–0.3 mL) targeting the IPBSN were performed on four lower limbs, followed by anatomical validation through dissection.</p> Results <p>The IPBSN was consistently identified as a honeycomb structure within a distinct fascial compartment. Both approaches effectively localized the nerve, with observed diffusion suggesting a potential compartment for selective nerve block. This dual-modality approach of ultrasound imaging and dissection enabled precise IPBSN localization, overcoming topographical variability relative to the sartorius muscle.</p> Conclusion <p>Distal ultrasound-guided IPBSN blocks show promise for knee pain management by achieving targeted analgesia while preserving muscle function. Further studies are needed to validate these techniques and refine injection protocols for clinical use.</p>