ObjectivesLocal anesthetic injection into the interspace between the popliteal artery and the posterior capsule of the knee (IPACK) has the potential to provide motor‐sparing analgesia to the posterior knee after total knee arthroplasty. The primary objective of this cadaveric study was to evaluate injectate spread to relevant anatomic structures with IPACK injection.MethodsAfter receipt of Institutional Review Board Biospecimen Subcommittee approval, IPACK injection was performed on fresh‐frozen cadavers. The popliteal fossa in each specimen was dissected and examined for injectate spread.ResultsTen fresh‐frozen cadaver knees were included in the study. Injectate was observed to spread in the popliteal fossa at a mean ± SD of 6.1 ± 0.7 cm in the medial‐lateral dimension and 10.1 ± 3.2 cm in the proximal‐distal dimension. No injectate was noted to be in contact with the proximal segment of the sciatic nerve, but 3 specimens showed injectate spread to the tibial nerve. In 3 specimens, the injectate showed possible contact with the common peroneal nerve. The middle genicular artery was consistently surrounded by injectate.ConclusionsThis cadaver study of IPACK injection demonstrated spread throughout the popliteal fossa without proximal sciatic involvement. However, the potential for injectate to spread to the tibial or common peroneal nerve was demonstrated. Consistent surrounding of the middle genicular artery with injectate suggests a potential mechanism of analgesia for the IPACK block, due to the predictable relationship between articular sensory nerves and this artery. Further study is needed to determine the ideal site of IPACK injection.