INTRODUCTION: Vulnerability factors like respiratory sinus arrhythmia (RSA) may help identify adolescents at risk for nicotine dependence. We examined if resting RSA and the acute effects of smoking on RSA was associated with cigarette smoking five years later among adolescents at high risk for smoking escalation and nicotine dependence. METHODS: Sixty-nine adolescents participated in a baseline laboratory session- RSA was collected before and after smoking a single cigarette ad libitum. Participants were then followed for five years. RESULTS: Lower pre-smoke resting RSA was related to higher past month smoking rate five years later, even after controlling for baseline smoking rate and other relevant covariates including gender, race/ethnicity, age of initiated use, and frequency of exercise at baseline (p=0.018). Exploratory analyses suggested resting RSA is an independent predictor of increased cigarette rate beyond other baseline predictors. CONCLUSIONS: Low resting RSA may be a vulnerability factor, helping to identify adolescents at risk for cigarette escalation.