Objectives Identifying patients at risk for impaired long-term survival after heart transplantation (HT) remains a clinical challenge. The aim of this analysis was to investigate whether the gene expression profiling test AlloMap® is related to long-term survival after HT. Methods 46 patients who underwent HT between 2006 and 2007 who were originally included into the CARGO II trial at our institution were investigated. Patients were divided in two groups according to an increase or decrease of the AlloMap® score between 6 and 9 months after HT. The primary endpoint of this study was long-term all-cause mortality. Results 23 patients showed an increase of the AlloMap® score between 6 and 9 months after HT whereas the remaining 23 patients presented with a decrease of the score. After a median follow-up time of 8.1 years (interquartile range 7.6–8.6), all-cause mortality was significantly elevated in patients with an AlloMap® increase compared with patients who showed a decrease of the score (log-rank p = 0.005). A ratio of the AlloMap® at 9 months to 6 months of 1.02 or less was associated with a negative predictive value for all-cause mortality of 100%. Conclusions Dynamic changes of the AlloMap® score between 6 and 9 months after HT were strongly related to all-cause long-term survival after HT. These results suggest that AlloMap® potentially displays a useful tool to estimate the patients’ risk for long-term mortality.