Delayed response to clinical deterioration of hospital inpatients is common. Deployment of an electronic automated advisory vital signs monitoring and notification system to signal clinical deterioration is associated with significant improvements in clinical outcomes but there is no evidence on the cost-effectiveness compared with routine monitoring, in the National Health Service (NHS) in the United Kingdom (UK). A decision analytic model was developed to estimate the cost-effectiveness of an electronic automated advisory notification system versus standard care, in adults admitted to a district general hospital. Analyses considered: (1) the cost-effectiveness of the technology based on secondary analysis of patient level data of 3787 inpatients in a before-and-after study; and (2) the cost-utility (cost per quality-adjusted life-year (QALY)) over a lifetime horizon, extrapolated using published data. Analysis was conducted from the perspective of the NHS. Uncertainty in the model was assessed using a range of sensitivity analyses. The study population had a mean age of 68 years, 48% male, with a median inpatient stay of 6 days. Expected life expectancy at discharge was assumed to be 17.74 years. (1) Cost-effectiveness analysis: The automated notification system was more effective (-0.027 reduction in mean events per patient) and provided a cost saving of -£12.17 (-182.07 to 154.80) per patient admission. (2) Cost-utility analysis: Over a lifetime horizon the automated notification system was dominant, demonstrating a positive incremental QALY gain (0.0287 QALYs, equivalent to ~10 days of perfect health) and a cost saving of £55.35. At a threshold of £20,000 per QALY, the probability of automated monitoring being cost-effective in the NHS was 81%. Increased use of cableless sensors may reduce cost-savings, however, the intervention remains cost-effective at 100% usage (ICER: £3,107/QALY). Stratified cost-effectiveness analysis by age, National Early Warning Score (NEWS) on admission, and primary diagnosis indicated the automated notification system was cost-effective for most strategies and that use representative of the patient population studied was the most cost-saving strategy. Automated notification system for adult patients admitted to general wards appears to be a cost-effective use in the NHS; adopting this technology could be good use of scarce resources with significance for patient safety. [Abstract copyright: Copyright: © 2024 Holmes et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.]