Objective assessment tools should standardize and reflect nurses' expert assessments. The Neonatal Pain, Agitation, and Sedation Scale (N-PASS) and the Neonatal Infant Pain Scale (NIPS) are valid measures of pain. The N-PASS also provides a sedation subscale. The objective of this study was to determine N-PASS clinical validity and utility by evaluating agreement of N-PASS scores with bedside nurses' assessments of pain/agitation and sedation in a 64-bed tertiary neonatal intensive care unit. Fifteen bedside nurses trained to use the N-PASS and the NIPS prospectively completed 202 pain/agitation and sedation assessments from a convenience sample of 88 infants, including chronically ventilated, medically fragile infants. N-PASS and NIPS scores were obtained simultaneously but independently of nurse investigators. Bedside nurses also made recommendations about infants' pain and sedation management. There was moderate agreement between N-PASS pain scores and nurses' recommendations (κ= 0.52), very strong agreement between N-PASS sedation scores and nurses' recommendations (κ= 0.99), and very strong associations between N-PASS pain and NIPS scores ( P < .001). Bedside nurse and independent investigator interrater reliability was good for N-PASS pain and NIPS scores (intraclass correlation coefficient [ICC] = 0.83, ICC = 0.85) and excellent for N-PASS sedation (ICC = 0.94). During 93% of assessments, bedside nurses reported that the N-PASS reflected the level of infant sedation well or very well. The N-PASS provides an easy-to-use, valid, and reliable objective measure of pain and sedation that reflects nurses' assessments. Additional studies using the N-PASS are needed to verify results and the influence of the N-PASS on pain and sedation management for medically fragile infants with chronic medical conditions.