Advanced glycation end products (AGEs) are associated with cardiovascular diseases. Whether the AGE levels change during myocardial reperfusion injury is currently unknown. The aim of our study was to investigate the dynamics of AGEs in myocardial reperfusion injury and to discuss potential reasons for these changes. The dynamics of AGEs, pentosidine and neopterin in the plasma of patients with acute myocardial infarction (AMI) treated using thrombolysis (n = 40) were analyzed. In addition, AGEs were measured in patients with open heart surgery (n = 12) and rabbits with induced AMI (n = 9). In all three studies of myocardial reperfusion injury, a significant decrease of AGEs was observed (by 26 ± 19% in patients with AMI, by 23 ± 14% in patients with open heart surgery and by 39 ± 10% in rabbits with AMI within 1 day of reperfusion; p < 0.05 in all studies). In additional studies, an association between lower AGEs and an activated immune system (R (2) = 0.09; p < 0.01) and fasting (decrease by 38%; p < 0.01) was shown. AGEs decrease in reperfusion injury of the heart. Indices pointing towards the involvement of immune system activation and fasting are presented. Further studies focusing on the underlying mechanism and on the clinical value of the observed dynamics of AGEs are needed.