Resynchronization therapy has become standard of care in patients with left bundle branch block (LBBB), congestive heart failure (CHF), and low ejection fraction (EF). In order to characterize the left ventricular (LV) function evolution in patients with LBBB and baseline preserved LVEF, records of all patients who visited an academic echocardiography laboratory during a period of 4 years were retrospectively investigated. Patients were included if they had a baseline EF >50%, LBBB on surface electrocardiography, and at least one follow-up echocardiogram no earlier than 3 months after the baseline study. The endpoint was the occurrence of EF deterioration to values ≤40%. Clinical variables associated with this outcome were identified. Forty-nine patients satisfied the entry criteria. Over a mean 13±8.5 months of follow-up (range 3 to 36), 8 patients (16%) experienced EF deterioration ≤40%. History of CHF prior to baseline echocardiogram and LV mass >300 g were associated with this phenomenon (P=.004 and P=.015, respectively), with a negative predictive value of 100% and 92%, respectively. Our data profiles a risk-stratification methodology in patients with LBBB and baseline EF >50% and possibly a triage strategy toward resynchronization therapy in this population.