Over 50,000 very low birth weight (VLBW) infants are born each year in the United States. Despite advances in care, these premature babies are subjected to long stays in a neonatal intensive care unit (NICU), and experience high rates of morbidity and mortality. In a large randomized controlled trial (RCT), heart rate characteristics (HRC) monitoring in addition to standard monitoring decreased all-cause mortality among VLBW infants by 22%. We sought to understand the cost-effectiveness of HRC monitoring to improve survival among VLBW infants. We performed a secondary analysis of cost-effectiveness of heart rate characteristics (HRC) monitoring to improve survival from birth to NICU discharge, up to 120 days using data and outcomes from an RCT of 3,003 VLBW patients. We estimated each patient's cost from a third-party perspective in 2021 USD using the resource utilization data gathered during the RCT (NCT00307333) during their initial stay in the NICU and applied to specific per diem rates. We computed the incremental cost-effectiveness ratio and used non-parametric boot-strapping to evaluate uncertainty. The incremental cost-effectiveness ratio of HRC-monitoring was $34,720 per life saved. The 95th percentile of cost to save one additional life through HRC-monitoring was $449,291. HRC-monitoring appears cost-effective for increasing survival among VLBW infants.