Background: Left bundle branch block (LBBB) is an important and independent determinant of mortality among patients with cardiovascular disease (CVD). Close follow-up and management of isolated LBBB to prevent cardiomyopathy is controversial. Methods: In this retrospective cohort study, patients with isolated LBBB, with no concomitant evident cardiac disease, or risk factors of heart failure with reduced EF such as hypertension or diabetes mellitus (DM) were included. The mean follow-up of the patients was 56 months. At the onset of the study, coronary angiogram and EF of the patients were normal. Patients with reduced EF underwent coronary angiogram at the end of their follow-up interval. Results: In this study, 36 patients, with the mean age 62.1 years (45-81) were followed. LV ejection fraction (EF) was reduced in 24 patients, and the other 11 patients continued to have a normal EF during the follow-up. The follow-up interval between the 2 groups was not statistically different (Mann-Whitney, P = 0.9). Most of the patients with reduced EF were male (Mann-Whitney, P = 0.01). New-onset HTN had a negative correlation with a decrease in EF% (Spearman correlation coefficient =-0.36, P = 0.031). Based on surface ECG parameters, 8 new notched-QRS were detected, all of which had decreased EF during follow-up. Conclusions: Not all patients with isolated LBBB develop cardiomyopathy at a definite time interval. Male gender, notched-QRS in ECG, and longevity of conduction delay are important predictors of cardiomyopathy among these patients. They may benefit from anti-remodeling drugs and routine close follow-ups with echocardiogram.