Information regarding the changes of iron regulation at the acute phase and during the first few months following acute reperfused ST-segment-elevation myocardial infarction (MI) is scarce. However, changes in hepcidin, the major regulatory protein responsible for iron homeostasis, and other partners of iron status may occur. We assayed iron, transferrin, ferritin and hepcidin serum concentrations in a subgroup of patients of the PREGICA patient collection 4±2 days (D4) and 6 months (M6) after a first ST+ MI with at least 3 akinetic LV segments at echocardiography performed at D4. Patients were classified as exhibiting myocardial hemorrhage (MH, n=8), microvascular obstruction (MVO, n=14), both (HVO, 47) or none of these deleterious conditions (C, n=18) according to MRI performed at D4, and as remodelers (R) or non-remodelers (NR) when their LVEDV increased (R) or did not change or decreased (NR) between D4 and M6, respectively. Serum iron concentration increased from D4 to M6 in all patients (P<0.0001) with larger increases in MH, MVO and HVO as compared to C patients (P<0.005) whereas transferrin concentration did not change, resulting in increased transferrin saturation coefficients. At D4, hepcidin concentration (ng/mL) was higher in MH (28.0±12.7), MVO (34.1±17.8) and HVO (31.6±27.1) patients than in C patients (17.4±11.6, P=0.05). From D4 to M6, it decreased to normal values in all patient groups (P<0.0002). This was associated with a decrease in ferritin concentration (P<0.01). There was a tendency for a more pronounced decrease in ferritin concentration in R than in NR patients (P=0.06). Our results indicate that iron homeostasis is altered shortly after a large ST+ MI. They suggest a role for MH, MVO and inflammation at the acute phase, responsible for increased hepcidin concentration, itself resulting in decreased iron stores and normalized hepcidin concentration on the long-term.