BACKGROUND: Autonomic dysfunction contributes to atrial fibrillation (AF). OBJECTIVE: We hypothesized that polysomnogram (PSG)-based heart rate variability (HRV) autonomic function biomarkers are associated with incident AF and these associations are modified by measures of sleep disordered breathing (SDB). METHODS: 2350 participants of a multi-center prospective study (Outcomes of Sleep Disorders in Older Men Study) without baseline AF underwent sleep studies with incident adjudicated AF follow up (8.0 +/- 2.6 years). Cox proportional hazard models were used to analyze sleep study-ECG spectral HRV indices [low and high frequency power (LF, HF), LF/HF] and time domain indices [mean of normal to normal beats (MNN), short and long term variability (STV, LTV) and STV/LTV] and premature atrial contractions (PACs) and incident AF (HR and 95% CI). Statistical interactions between HRV and SDB were examined. Models were adjusted for age, race, body mass index, waist circumference, cardiac medications, co-morbid diseases, alcohol use and study site. RESULTS: Lower LF/HF and lower LF were associated with higher AF incidence (LF/HF Q1 vs. Q4: 1.46, 1.02-2.08, LF Q1 vs. Q4: 1.46, 1.02-2.10). Higher STV/LTV was associated with an increased risk of AF (p-trend= 0.028). The highest PAC quartile had a 3-fold increased AF risk (2.99, 1.94-4.62) compared to the lowest quartile. A significant interaction of obstructive apnea was observed in the LF-AF relationship (0.045). CONCLUSIONS: Sleep-related reduced sympathovagal balance (LF/HF) and increased atrial ectopy are independently associated with future AF; a relationship modified by obstructive apnea.