© 2015 American Heart Association, Inc. Background and Purpose - Premature ventricular complexes (PVCs) detected from long-term ECG recordings have been associated with an increased risk of ischemic stroke. Whether PVCs seen on routine ECG, commonly used in clinical practice, are associated with an increased risk of ischemic stroke remains unstudied. Methods - This analysis included 24 460 participants (aged, 64.5+9.3 years; 55.1% women; 40.0% blacks) from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were free of stroke at the time of enrollment. PVCs were ascertained from baseline ECG (2003-2007), and incident stroke cases through 2011 were confirmed by an adjudication committee. Results - A total of 1415 (5.8%) participants had at least 1 PVC at baseline, and 591 developed incident ischemic stroke during an average (SD) follow-up of 6.0 (2.0) years. In a cox proportional hazards model adjusted for age, sex, race, geographic region, education, previous heart disease, systolic blood pressure, blood pressure-lowering medications, current smoking, diabetes mellitus, left ventricular hypertrophy by ECG, and aspirin use and warfarin use, the presence of PVCs was associated with 38% increased risk of ischemic stroke (hazard ratio [95% confidence interval], 1.38 [1.05-1.81]). Conclusions - PVCs are common on routine screening ECGs and are associated with an increased risk of ischemic stroke.