Local anesthetic (LA) injection outside the sheath in epineural or paraneural connective tissue is considered safe practice among regional anesthesiologists. There is limited evidence as to whether neurological complications occur if LA is injected inside the sheath (subepineural – intraneural). We performed ultrasound guided injections at the level of undivided sciatic nerve in four amputated lower limbs. In two specimens, LA was injected in epineural connective tissue (paraneural tissue) and in another two specimens by penetrating the outer nerve sheath (hyperechoic epineurium). Ultrasonography demonstrated an increase in the size of nerve and macroscopic findings revealed fascicular tracings with sub-epineural injections. Limbs were sent for histological analysis in formalin containers. Pathologist performed the analysis which demonstrated an intact perineurium and a breach in the epineurium. We conclude that sub-epineural injections are unsafe and injection should be done in paraneural tissue to ensure safety and avoid unwanted neurological sequelae after the block.