The prognosis of progressive ophthalmoplegia in patients with large-scale mitochondrial DNA deletions is highly variable and almost unpredictable. The risk to develop cardiac involvement and sudden cardiac death is strikingly high, especially in patients with Kearns–Sayre syndrome (KSS). The most typical cardiac complications of the disease are conduction defects, which usually begin with left anterior fascicular block with or without right bundle branch block (RBBB), progressing sometimes rapidly to complete atrioventricular block. Other cardiac manifestations reported are first or second degree of AV block, QT prolongation, torsades de pointes ventricular tachycardia, and rarely dilated cardiomyopathy. Most frequently syncope, sometimes even sudden cardiac death, is the first clinical sign of the cardiac disease in KSS. Due to these life-threatening cardiac conditions, patients should be carefully monitored for cardiac signs and symptoms and pacemaker implantation should be suggested early to avoid sudden cardiac arrest in KSS. Here, we present two cases of KSS with life-threatening syncope due to complete atrioventricular block. To emphasize the importance of an early pacemaker implantation, we review the literature on cardiac complications in KSS in the last 20 years. In almost all of the reviewed cases, ophthalmoplegia or ptosis was present before the cardiac manifestations. In most of the cases, syncope was the first symptom of the cardiac involvement. There was no correlation between the age of the onset of the disease and the onset of cardiac manifestations. With our current report, we increase awareness for life-threatening cardiac complications in patients with KSS.