BACKGROUND:Acute allograft rejection appears to be associated with increases in QT/QTc intervals. OBJECTIVES:To determine the relationship between acute allograft rejection and electrocardiogram changes in patients undergoing an orthotopic heart transplant. METHODS:The study population comprised 220 adult patients undergoing heart transplant and enrolled in the NEW HEART study. Electrocardiograms obtained within 72 hours of endomyocardial biopsy were analyzed; electrocardiograms obtained fewer than 10 days after transplant surgery were excluded. Repeated-measures analysis was performed with statistical models including effects for rejection severity (mild and moderate/severe) and time trends independent of rejection status. RESULTS:The 151 male and 69 female transplant recipients (mean age [SD], 54 [13] years) had 969 biopsy/electrocardiogram pairs: 677 with no rejection, 280 with mild rejection, and 12 with moderate/severe rejection. Moderate to severe organ rejection was associated with significant increases in QRS duration (P < .001), QT (P = .009), QTc (P = .003), and PR interval (P = .03), as well as increased odds of right bundle block branch (P = .002) and fascicular block (P = .009) occurring. CONCLUSIONS:Moderate to severe acute allograft rejection was associated with electrocardiographic changes after transplant surgery. Studies are needed to assess the value of computerized electrocardiogram measurement algorithms for detecting acute allograft rejection.