Aim: Alarm fatigue is a well-recognized patient safety concern in intensive care settings. Decreased nurse responsiveness and slow response times to alarms are the potentially dangerous consequences of alarm fatigue. The aim of this study was to determine the factors that modulate nurse responsiveness to critical patient monitor and ventilator alarms in the context of a private room neonatal intensive care setting. Methods: The study design comprised of both a questionnaire and video monitoring of nurse-responsiveness to critical alarms. The Likert scale questionnaire, comprising of 50 questions across thematic clusters (critical alarms, yellow alarms, perception, design, nursing action, and context) was administered to 56 nurses (90% response rate). Nearly 6000 critical alarms were recorded from 10 infants in approximately 2400 hours of video monitoring. Logistic regression was used to identify patient and alarm-level factors that modulate nurse-responsiveness to critical alarms, with a response being defined as a nurse entering the patient’s room within the 90s of the alarm being generated. Results: Based on the questionnaire, the majority of nurses found critical alarms to be clinically relevant even though the alarms did not always mandate clinical action. Based on video observations, for a median of 34% (IQR, 20–52) of critical alarms, the nurse was already present in the room. For the remaining alarms, the response rate within 90s was 26%. The median response time was 55s (IQR, 37-70s). Desaturation alarms were the most prevalent and accounted for more than 50% of all alarms. The odds of responding to bradycardia alarms, compared to desaturation alarms, were 1.47 (95% CI = 1.21–1.78; <0.001) while that of responding to a ventilator alarm was lower at 0.35 (95% CI = 0.27–0.46; p <0.001). For every 20s increase in the duration of an alarm, the odds of responding to the alarm (within 90s) increased to 1.15 (95% CI = 1.1–1.2; p <0.001). The random effect per infant improved the fit of the model to the data with the response times being slower for infants suffering from chronic illnesses while being faster for infants who were clinically unstable. Discussion: Even though nurses respond to only a fraction of all critical alarms, they consider the vast majority of critical and yellow alarms as useful and relevant. When notified of a critical alarm, they seek waveform information and employ heuristics in determining whether or not to respond to the alarm. Conclusion: Amongst other factors, the category and duration of critical alarms along with the clinical status of the patient determine nurse-responsiveness to alarms.