To compare the knowledge and problem-solving, communication, and clinical skills of graduating neonatal nurse practitioners (NNPs) and pediatric residents, a cohort study was conducted in a 33-bed tertiary-level neonatal intensive care unit in a 400-bed teaching hospital affiliated with a faculty of health sciences. Participants were all (n = 10) NNP graduates from the first 3 years of the educational program and 13 (87%) of 15 second-year pediatric residents. One hundred multiple-choice questions and 20 radiographic slides were used to test knowledge; a semistructured oral examination tested problem-solving skills; three simulated interactions with parents tested communication skills; and seven simulated procedures tested clinical skills. Graduating NNPs scored similarly to the pediatric residents on the multiple-choice questions (difference -3.4%; 95% confidence interval [CI] around difference -9.7, 2.9), radiographs (difference -1.4%; 95% CI -11.5, 8.7), oral examination (difference 2.8%; 95% CI -11.1, 16.7), communication skills (simulated parents assessment: difference 0.8%; 95% CI -4.2, 5.7; expert observer assessment: difference 5.8%; 95% CI -2.8, 14.3), and clinical skills (difference 7.4%; 95% CI -5.5, 20.2). The NNPs about to graduate from their educational program showed knowledge and problem-solving, communication, and clinical skills equivalent to those of second-year pediatric residents and are thus likely to deliver comparable care in the clinical setting. The results support the adoption of the NNP role.