Background: Whether autonomic nerve activity is important in the development of pacing-induced sustained atrial fibrillation (AF) is unclear. Objective: The purpose of this study was to test the hypothesis that patterns of baseline autonomic nerve activity are important in the development of pacing-induced sustained AF. Methods: Radiotransmitters were implanted in 12 ambulatory dogs to record left stellate ganglion nerve activity (SGNA) and vagal nerve activity (VNA). Sustained (>48 hours) AF was induced with intermittent rapid atrial pacing. Results: At baseline (before pacing), 1-minute integrated nerve activity between SGNA and VNA demonstrated either a single linear relationship with excellent correlation (group 1, N = 3, r = 0.816 ± 0.105) or nonlinear relationships with poor correlation (group 2, N = 9, r = 0.316 ± 0.162, P <.05 vs group 1). Group 1 dogs had higher VNA (97.0 ± 11.5 mV-s) compared to group 2 (33.4 ± 21.7 mV-s, P <.001). Group 1 dogs had more frequent sympathovagal co-activation episodes than did group 2 (50 ± 19 per day vs 15 ± 6 per day, P <.05) and more paroxysmal atrial tachycardia (PAT; 5 ± 1 per day vs 2 ± 1 per day, P <.05) at baseline. Sustained AF occurred after 16 ± 4 days (range 1320 days) of pacing in group 1 and after 46 ± 18 days (range 2372 days) of pacing in group 2 (P <.05). In the week before development of sustained AF, VNA of group 2 dogs was significantly increased compared to baseline (P <.05). Conclusion: Ambulatory dogs with good linear sympathovagal correlation and higher vagal tone at baseline have more PAT episodes at baseline and faster induction of sustained AF by rapid pacing. Rapid atrial pacing increased the VNA of the remaining dogs before induction of sustained AF.