9064 Background: Methadone (ME) has been used increasingly for pain control and for maintenance in drug addiction programs. Its use is increasing in cancer patients (pts), mainly as part of opioid rotation. Some recent reports suggest that ME may prolong QTc interval and cause torsade de pointes in pts on high dose ME. The purpose of our study was to determine the effect of initiation of ME on QTc interval in pts with cancer pain. Methods: We enrolled 101 pts in this prospective study. These pts had never been on ME before. Pts were followed clinically and electrocardiographically for QTc changes from baseline. EKG was obtained at baseline (QTc0), 2 (QTc2), 4 (QTc4), and 8 (QTc8) weeks. We recorded other contributing factors for QTc prolongation such as medication interactions with ME and electrolyte disturbances. QTc is prolongation is defined as > 430 ms in males and > 450 ms in females. In our study, significant QTc prolongation was defined as = 10% increase from baseline or QTc = 500 msec. Results: 74 pts (73%) had normal QTc (group A) and 27 pts (27%) had prolonged QTc (group B) at baseline. Significant increase in QTc in group A males occured in 1 of 16 (6%) at week 2, 2 of 10 (20%) at week 4, and 0 of 8 (0%) at week 8. Significant increase in QTc in group A females occured in 3 of 32 (10%) at week 2, 1 of 21 (5%) at week 4, and 0 of 12 (0%) at week 8. These pts had multiple contributing factors for QTc prolongation. QTc > reference for males occured in 6 of 16 (37%) at week 2, 4 of 10 (40%) at week 4, and 1 of 8 (12%) at week 8; in females, 1 of 32 (3%) at week 2, 3 of 21 (14%) at week 4, and 1 of 12 (8%) at week 8 ( Table 1 ). 2 of 27 pts (7%) from group B had a significant prolongation at week 2: one of them had an increase from 498 to 509 ms, then to 512 at week 4 and 486 at week 8. Conclusions: Baseline prolonged QTc is a common finding. QTc prolongation = 500 ms is rare in pts receiving ME for cancer pain. No data exists for other opioids. There was one case of temporary increase in QTc > 500 ms. There was no evidence of severe arrhythmias or torsade de pointes clinically or on EKG. ME dose was = 50 mg/day in the majority of these pts. [Table: see text] No significant financial relationships to disclose.