To investigate heart rate and respiratory sinus arrhythmia (RSA) as markers of developmental outcome, infant ECG and 3 year outcome were assessed in 41 very low birth weight (< 1,500 g) infants. Measures of mean heart rate and RSA, and the maturational shifts in their values from 33 to 35 weeks gestational age, were recorded. RSA measures predicted 3 year outcome beyond the effects of birth weight, medical risk, and socioeconomic status. Higher RSA was associated with better social skills, whereas greater RSA maturation was associated with better mental processing and gross motor skills. Lower heart rate was associated with better behavior regulation and social skills, whereas greater maturational decreases were associated with better gross motor skills. Dividing the sample into groups of infants with birth weights less than 1,000 g and those with birth weights over 1,000 g, RSA maturation emerged a strong predictor of mental processing, knowledge base, and gross motor skills in the former. A measure of joint maturation of RSA and heart rate was associated with better behavior regulation at 3 years, as measured by Child Behavior Checklist and Parenting Stress Index scores, for this group. The findings directly respond to the need for physiological variables in the prediction of outcome in high-risk infants.