Background <p>Following acute myocardial infarction (AMI), patients face an approximately 20% risk of experiencing another cardiovascular event within the first year. Engaging in physical activity (PA) aids in the management of risk factors, improves quality of life, and reduces the risk of cardiac recurrence and mortality. MicroRNAs (miRNAs) are post-transcriptional gene regulators that play a crucial role in the development of atherosclerosis. We aimed to monitor levels of atherogenic cell-free circulating miRNAs in response to PA in patients after AMI.</p> Methods <p>A total of 29 patients diagnosed with AMI were enrolled in our randomized crossover study (10% women; mean age 52.3 ± 11&#xa0;years). Patients were assigned to either a control or intervention group, crossing over after three months. Blood plasma was collected during hospitalization after AMI diagnosis, at the end of the first month, and after each three-month intervention period. Nine selected atherogenic circulating miRNAs were measured using quantitative PCR.</p> Results <p>Most of the analyzed miRNAs declined during the year following AMI (all <i>P</i> &lt; 0.0005), except for miR-142-5p, which increased. PA did not impact the plasma levels of any measured miRNAs, except for a slight reduction in miR-146a-5p (<i>P</i> = 0.08). Multiple linear regression indicated an inverse correlation between miR-146a-5p and VO₂max (<i>P</i> = 0.02), and between miR-130a-3p and active body mass (<i>P</i> = 0.006) and basal metabolism (<i>P</i> &lt; 0.05).</p> Conclusion <p>PA in post-AMI patients may affect circulating miRNAs related to inflammation and adipogenesis.</p>