Background: The aim of this study was to evaluate the course of Thrombolysis in Myocardial Infarction (TIMI) frame count (TIMI FC) and myocardial perfusion grade (TIMI MPG) in heart transplant recipients and whether these parameters could predict mortality. Methods: Sixty-two heart transplant recipients were enrolled in this study. All patients had coronary angiography at baseline and at 1 year, which were evaluated for TIMI FC and TIMI MPG. Also, 50 vessels in 35 patients were analyzed with volumetric intravascular ultrasound (IVUS) at baseline and at 1 year. Rejection episodes and mortality were recorded during the follow-up period. Results: The mean follow-up interval was 51.5 ± 17.2 months (range 12.2 to 78.4 months). TIMI FCs of all three coronary arteries and global TIMI FC (gTIMI FC) significantly increased from baseline during the first year (p < 0.0001). TIMI MPG deteriorated significantly (p < 0.0001 for left anterior descending and circumflex coronary arteries, p = 0.002 for right coronary artery). There was no correlation between changes in TIMI FC and progression of transplant vasculopathy as assessed by IVUS. Episodes of Grade ≥3A rejection were significantly more frequent in the stable gTIMI FC group (p = 0.03). Mortality rate was significantly higher in the group with increasing gTFC (p = 0.02). Conclusions: gTIMI FCs and TIMI FCs of coronary arteries increase, and TIMI MPG gradually deteriorates during the first year after transplantation. Mortality rate is significantly higher in patients whose gTIMI FC increases from baseline. Change in gTIMI FC is a simple quantitative predictor of long-term mortality in heart transplant recipients.