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Background: Clinical alarm systems safety is a national concern, specifically in intensive care units (ICUs) where alarm rates are known to be the highest. Interventional projects that examined the effect of changing default alarm settings on overall alarm rate and on clinicians’ attitudes and practices toward clinical alarms and alarm fatigue are scarce. Objective: To examine if (1) a change in default alarm settings of the cardiac monitors and (2) in-service nursing education on cardiac monitor use in an ICU would result in reducing alarm rate and in improving nurses’ attitudes and practices toward clinical alarms. Methods: This quality improvement project took place in a 20-bed transplant/cardiac ICU with a total of 39 nurses. We implemented a unit-wide change of default alarm settings involving 17 parameters of the cardiac monitors. All nurses received an in-service education on monitor use. Alarm data were collected from the audit log of the cardiac monitors 10 weeks before and 10 weeks after the change in monitors’ parameters. Nurses’ attitudes and practices toward clinical alarms were measured using the Healthcare Technology Foundation National Clinical Alarms Survey, pre- and postintervention. Results: Alarm rate was 87.86 alarms/patient day (a total of 64,500 alarms) at the preintervention period compared to 59.18 alarms/patient day (49,319 alarms) postintervention ( P =.01). At baseline, Arterial Blood Pressure (ABP), Pair Premature Ventricular Contractions (PVCs), and Peripheral Capillary Oxygen Saturation (SpO2) alarms were the highest. ABP and SpO2 alarms remained among the top three at the postproject period. Out of the 39 ICU nurses, 24 (62%) provided complete pre- and postproject survey questionnaires. Compared to the preintervention survey, no remarkable changes in the postproject period were reported in nurses’ attitudes. Themes in the narrative data were related to poor usability of cardiac monitors and the frequent alarms. The data showed great variation among nurses in terms of changing alarm parameters and frequency of replacing patients' electrodes. Despite the in-service, 50% (12/24) of the nurses specified their need for more training on cardiac monitors in the postproject period. Conclusions: Changing default alarm settings and standard in-service education on cardiac monitor use are insufficient to improve alarm systems safety. Alarm management in ICUs is very complex, involving alarm management practices by clinicians, availability of unit policies and procedures, unit layout, complexity and usability of monitoring devices, and adequacy of training on system use. The complexity of the newer monitoring systems requires urgent usability testing and multidimensional interventions to improve alarm systems safety and to attain the Joint Commission National Patient Safety Goal on alarm systems safety in critical care units. [JMIR Hum Factors 2016;3(1):e1]