Abstract: Although fat grafting is frequently used in plastic surgery practice, debate about the viability of the graft still persists owing to its questionable long-term success. The ultimate aim is to obtain long-term graft viability. Vascularization of the graft is essential for this purpose. The effects of 2 different local anesthetic preparations frequently used during harvesting of fat grafts on long-term graft survival were compared with angiogenesis and volumetric measurements. Twenty-four male Wistar rats were divided into 3 groups. The inguinal region was selected as the fat graft donor site. The first group was injected with isotonic saline, the second was injected with lidocaine plus epinephrine, and the third was injected with prilocaine. Fat grafts were implanted into the dorsal regions of rats, and volumetric measurements were performed initially and on days 30 and 180 at which microvascular angiogenesis were also analyzed. Microvascular angiogenesis was assessed both with the reverse transcription–polymerase chain reaction and immunohistochemistry through determination of vessels stained with factor VIII. No significant difference was obtained between the 3 groups in graft volume or microvascular angiogenesis at any stage of the study. Results from this experimental study indicate that there is no negative effect of lidocaine plus epinephrine or prilocaine on microangiogenesis and the survival of fat grafts.