Objective: To test the hypothesis that heart rate characteristics (HRC) monitoring improves neonatal outcomes. Study design: We conducted a two-group, parallel, individually randomized controlled clinical trial of 3003 very low birth weight infants in 9 neonatal intensive care units. In one group, HRC monitoring was displayed; in the other, it was masked. The primary outcome was number of days alive and ventilator-free in the 120 days after randomization. Secondary outcomes were mortality, number of ventilator days, neonatal intensive care unit stay, and antibiotic use. Results: The mortality rate was reduced in infants whose HRC monitoring was displayed, from 10.2% to 8.1% (hazard ratio, 0.78; 95% CI, 0.61-0.99; P =.04; number needed to monitor = 48), and there was a trend toward increased days alive and ventilator-free (95.9 of 120 days compared with 93.6 in control subjects, P =.08). The mortality benefit was concentrated in infants with a birth weight <1000 g (hazard ratio, 0.74; 95% CI, 0.57-0.95; P =.02; number needed to monitor = 23). There were no significant differences in the other outcomes. Conclusion: HRC monitoring can reduce the mortality rate in very low birth weight infants. © 2011 Mosby Inc. All rights reserved.