We compared the incidence of left ventricular systolic dysfunction (LVSD) among patients with left bundle branch block (LBBB) to a matched cohort of patients with a narrow QRS duration <120 ms (NQRS). We hypothesized patients with preserved ejection fraction (EF) ≥50% and LBBB would have higher incidence of LVSD compared with a matched population of NQRS patients. Patients with LBBB on electrocardiogram within 30 days of a baseline echocardiogram with EF ≥50%, who had at least 1 follow-up echocardiogram ≥6 months later, were matched 1:1 on risk factors for cardiomyopathy to patients with NQRS. Incident LVSD was defined as a decline in EF to ≤45% on follow-up echocardiogram, or heart transplant, receipt of a cardiac device for LVSD (defibrillator or biventricular pacemaker), or implantation of a left ventricular assist device ≥6 months post baseline echocardiogram. Relative risk was calculated using conditional Poisson regression techniques. The final study cohort consisted of 188 patients, 94 with LBBB and 94 with NQRS. On follow-up, progression to LVSD was noted in 36% of LBBB patients and 10% of NQRS patients. The relative risk for LVSD in patients with LBBB was 3.78 (95% confidence interval = 1.98 to 7.19). In conclusion, there is a strong association between LBBB and the subsequent development of LVSD independent of common risk factors for cardiomyopathy.