Background: Dual-chamber pacemakers restore AV synchrony compared with ventricular pacemakers, but the effects on health-related quality of life (QOL) are uncertain. Objectives: The purpose of this study was to assess the effect of pacemaker implantation, clinical factors, and pacing mode on QOL. Methods: The Mode Selection Trial (MOST) randomized 2,010 patients with sinus node dysfunction to rate-modulated right ventricular (VVIR) or dual-chamber (DDDR) pacing. A longitudinal analysis of serial QOL measures (Short Form-36 [SF-36], Specific Activity Scale, and time trade-off utility) was performed. In patients who crossed over from VVIR to DDDR because of severe pacemaker syndrome, the last known QOL prior to crossover was carried forward. Results: Pacemaker implantation resulted in substantial improvement in almost all QOL measures. Subjects 75 years or older experienced significantly less improvement in functional status and physical component summary scores than did younger subjects. In longitudinal analyses of the effect of pacing mode on QOL, significant improvement in three SF-36 subscales was observed with DDDR pacing compared with VVIR pacing: role physical [62.8 points (95% confidence interval [CI] 60.2, 65.5) vs 56.4 (95% CI 53.7, 59.1)], role emotional [85.0 (95% CI 82.9, 87.0) vs 81.9 (95% CI 79.9, 84.0)], and vitality [51.8 (95% CI 50.3, 53.3) vs 49.3 (95% CI 47.8, 50.7)], but not in other SF-36 subscales, the Specific Activity Scale, or utilities. The gains in QOL were larger than the declines associated with 1 year of aging but smaller than those associated with heart failure. Conclusion: Pacemaker implantation improved health-related QOL. The mode selected was associated with much smaller, but significant, improvements in several domains, particularly role physical function. © 2006 Heart Rhythm Society.