Circumcision is a frequently performed surgical procedure in neonates. Given the reluctance of some health-care providers to use a dorsal penile nerve block (DPNB) during circumcision, coupled with our desire to promote adequate pain control in neonates, we performed a prospective, blinded, randomized control trial to compare the efficacy of DPNB and a less invasive form of local anesthesia (EMLA cream) for reduction of pain during circumcision. The study population consisted of neonates ready for discharge from the NICU at Strong Memorial Hospital, a 52-bed facility serving the 11 county Finger Lakes region of NY. After parental consent, infants were randomized to receive either DPNB (0.7-1.0cc 1% lidocaine, sc, 3 min prior to circ) or EMLA (0.5g topically, 1h prior to circ). Circs were performed by a single individual. Infants were videotaped (from the waist up) and vital signs monitored. Tapes were reviewed and scored at six specified events during the procedure using a modified Neonatal Infant Pain Scale (NIPS) (min score 0; max 6) by a second individual, and behavioral and physiologic data were collected and analyzed by a third individual, both unaware of the infant's group assignment. Using the average NIPS score as the main outcome variable, to achieve a 5% significance and 80% power, sample size was 22 patients in each group. A third, nonrandomized group of infants who were circumcised by an Ob, without any anesthesia, was also taped and scored (n=14). Of 50 infants randomized, 6 were not included in analysis because of faulty recording equipment. NIPS scores were significantly lower in DPNB infants(2.4±0.3) compared with EMLA infants (4.9±0.3), p<.001. There was also a significant increase in heart rate over the duration of the circ in EMLA, but not in DPNB infants, p<.001. Infants receiving either form of anesthesia had significantly lower NIPS scores compared with infants circumcised without anesthesia, all of whom scored 6 throughout the procedure. There were no significant morbidities in any of the treatment groups. Thus, DPNB provides better pain amelioration than does EMLA cream; however, there may be some benefit provided by EMLA compared with no anesthesia during neonatal circumcision.