Introduction: Frequent premature ventricular contractions (PVC's) limit effective delivery of cardiac resynchronization therapy (CRT). However, neither the burden nor morphology of PVC's is well defined in patients with ischemic (ICM) and non-ischemic (NICM) cardiomyopathy. Methods: In MADIT-CRT, 947 patients enrolled in the CRT-D arm underwent 24-hour 12-lead Holter monitoring. Patients with >5000 PVC's were identified and the morphology of PVC's in each of these patients was assessed. Based on previously published ECG criteria, we characterized PVC's to originate from the RV or LV outflow tract, sinus of Valsalva, or a non-outflow tract location. Results: A total of 146 (15%) patients were identified, of whom 88 (60%) had ICM and 58 (40%) had NICM. The median total PVC count in ICM patients was 8807 as compared to 8950 in NICM patients, p=NS. PVC's with a LBBB morphology occurred in 34 (39%) ICM patients and 33 (57%) of NICM patients, p=0.03. In addition, RVOT appearing PVC's were significantly more frequent in NICM patients (19 (33%) vs. 11 (13%) in ICM patients, p=0.003). There was no difference in the number of PVC's that appeared to originate from the LVOT [ICM vs. NICM, 15 (17%) vs. 9 (16%), p=NS] or from the sinus of Valsalva [ICM vs. NICM 9 (10%) vs. 8 (14%), p=NS]. Non-outflow tract appearing PVC's were significantly more common in patients with ICM when compared to patients with NICM, 53 (60%) vs. 22 (38%), p=0.008. Conclusions: In 15% of patients undergoing CRT implantation, >5000 PVCs were observed. While there was no difference in the burden of PVC between ICM and NICM patients, there were significant differences in morphology (and thus site of origin) of PVC's in the 2 groups of patients. These data may have implications, especially in patients in whom catheter ablation is necessary to eliminate PVC's in order to maximize CRT.