Alarm fatigue is a practice problem that applies to hospitalized patients and the nurses who care for them. Addressing alarm fatigue is important to promote alarm safety and to decrease the risk of patient harm or death. The purpose of this study was to decrease alarm fatigue and improve alarm safety in a regional neonatal intensive care unit (RNICU). Guided by the conceptual model for alarm fatigue and alarm safety, this study addressed whether or not alarm management protocols designed to decrease false and nuisance alarms in the physiological monitoring of neonates improve alarm safety via decreased alarm burden and alarm fatigue as evidenced by statistically significant reductions in false and nuisance alarms. A quantitative, time series quasi-experimental design was used with 4 waves of data collection. One wave was baseline data collected preintervention, and 3 waves of data were postprotocol implementation to obtain an initial indication of sustainability. Alarm observation data collection sheets were developed and used to track numbers and types of alarms pre- and post-protocol implementation. The data analysis showed statistically significant decreases in both false alarms and nuisance alarms related to the physiological monitoring protocol and lead changing protocol. Overall, high protocol adherence was noted, and the total number of alarms per hour per bed was reduced by 42% (p < .001), 46% (p < .001), and 50% (p < .001) from baseline at Weeks 2, 4, and 6, respectively. Implications from this study include impact on practice and policy, direction for future study, and a call for social change to promote alarm safety in the care of neonates.