Purpose: A mixture of 2% lidocaine with epinephrine and bupivacaine was developed to achieve the fast-onset anesthetic effect of lidocaine and the long-lasting effect of bupivacaine. The authors compared pain scores between 2% lidocaine, 2% lidocaine with epinephrine, and 2% lidocaine with epinephrine-bupivicaine mixture during local anesthesia for eyelid surgeries. Methods: This was a double-blind, randomized, prospective, comparative study. In total, 120 consecutive patients (43 males, 77 females, mean age = 47.2 +/- 21.2) who underwent bilateral eyelid surgery under subcutaneous anesthesia were asked to report pain scores for each eye during the first injection of anesthesia. Each patient was randomly assigned to receive 1 of the 3 anesthetic agents in 1 eyelid, and 1 of the remaining 2 agents in the other. Results: The pH values of the 2% lidocaine, 2% lidocaine with epinephrine, and 2% lidocaine with epinephrine-bupivicaine mixture were 6.23 +/- 0.21, 4.21 +/- 0.37, and 3.87 +/- 0.19, respectively. The pain scores of each were 4.3 +/- 1.8, 5.1 +/- 1.8, and 5.7 +/- 1.9, respectively. The 2% lidocaine with epinephrine produced a statistically significantly higher pain score than 2% lidocaine (p = 0.044, generalized estimating equation method). The mixture also showed a significantly higher pain score than 2% lidocaine (p = 0.003, generalized estimating equation method). Conclusions: Epinephrine seemed to increase subjective pain scores. Compared with 2% lidocaine with epinephrine, 2% lidocaine with epinephrine-bupivicaine mixture was not significantly different in terms of subjective symptoms or pH.