Dual-chamber pacemaker insertion (PI) has been found to reduce the recurrence of neurally mediated syncope (NMS) in 3 randomized trials. However, the long-term benefits of PI are unknown. To assess the natural history of NMS, we followed a cohort of 40 patients who underwent PI for frequent NMS for 46 to 75 months. We assessed the reduction in syncope frequency after PI and the time to first recurrence of syncope. Sixty months after PI, 32.5% of patients remained free of NMS. The frequency of syncope decreased from 0.46 to 0.06 spells/month (before to after PI, p = 0.04). Two groups of patients were identified, with responders to PI defined as having a 75% decrease in the frequency of NMS. Responders (n = 22) experienced a significant decrease in the frequency of NMS (0.31 to 0.01 spells/month, p <0.0001), whereas nonresponders did not experience a similar reduction (p = 0.8). Responders could not be identified by either baseline or tilt-test parameters. Patients without an early recurrence of syncope after PI (within 6 months) experienced a significant reduction in the frequency of NMS (0.24 to 0.02 spells/month, p = 0.0002), although the reduction was not significant (p = 0.3) in patients with an early recurrence of syncope. Some, but not all, patients respond to permanent PI for NMS. The long-term benefit of permanent PI can be predicted by timing of the first recurrence of syncope, but not by preimplantation factors.