Ventricular premature complexes (VPCs) during exercise have long been believed to be harbingers of increased mortality. A recent study has shown that VPCs during the recovery phase of a treadmill exercise test are more predictive of mortality than VPCs that develop during exercise. However, no study to date has examined the relation of VPCs in recovery to the presence of ischemia on myocardial perfusion imaging. We examined the database of perfusion imaging at the Duke University Medical Center from September 1993 to July 2003. We examined the incidence of VPCs during exercise, during the recovery phase, and during the 2 phases. Logistic regression modeling was used to evaluate the significance of VPCs during stress and during recovery in predicting ischemia. VPCs developed during recovery in 561 of 2,828 patients (19.8%). Compared with patients without VPCs during recovery, those with VPCs during recovery were more likely to have a history of hypertension (64.0% vs 56.9%, p = 0.002) and previous coronary artery bypass grafting (25.3% vs 17.1%, p = 0.001). They were also more likely to be older, men, and Caucasian, and to have 3-vessel coronary artery disease (31.9% vs 21.0%, p = 0.001). After adjusting for differences in patient characteristics, VPCs during recovery were significantly associated with ischemia (odds ratio 1.27, 95% confidence interval 1.04 to 1.56, p = 0.017), whereas VPCs during stress were not (p = 0.128). In conclusion, VPCs during the recovery phase of an exercise study are predictive of ischemia on myocardial perfusion imaging.