The neonatal mouse heart has a transient regenerative capacity that is lost by 7 days of age. This study shows that 1-day-old mice can regenerate their hearts after partial surgical resection, with cardiomyocyte proliferation and minimal fibrosis, distinguishing it from adult heart repair. Genetic fate mapping indicates that most regenerated cardiomyocytes originate from preexisting cells. Echocardiography 2 months post-surgery showed normal systolic function in the regenerated ventricular apex. In contrast, 7-day-old mice failed to regenerate and developed fibrosis, suggesting that the regenerative capacity is lost within the first week of life. The neonatal heart's regenerative potential is linked to cardiomyocyte proliferation and dedifferentiation, which is lost when cardiomyocytes exit the cell cycle. The study highlights the importance of understanding the mechanisms behind this transient regenerative capacity in mammals, as it may inform future regenerative therapies. The findings suggest that the loss of regenerative potential in adult hearts may be due to intrinsic cell cycle block or loss of mitogenic stimuli. Further research is needed to determine the exact mechanisms by which the mammalian heart switches off this regenerative capacity after birth.The neonatal mouse heart has a transient regenerative capacity that is lost by 7 days of age. This study shows that 1-day-old mice can regenerate their hearts after partial surgical resection, with cardiomyocyte proliferation and minimal fibrosis, distinguishing it from adult heart repair. Genetic fate mapping indicates that most regenerated cardiomyocytes originate from preexisting cells. Echocardiography 2 months post-surgery showed normal systolic function in the regenerated ventricular apex. In contrast, 7-day-old mice failed to regenerate and developed fibrosis, suggesting that the regenerative capacity is lost within the first week of life. The neonatal heart's regenerative potential is linked to cardiomyocyte proliferation and dedifferentiation, which is lost when cardiomyocytes exit the cell cycle. The study highlights the importance of understanding the mechanisms behind this transient regenerative capacity in mammals, as it may inform future regenerative therapies. The findings suggest that the loss of regenerative potential in adult hearts may be due to intrinsic cell cycle block or loss of mitogenic stimuli. Further research is needed to determine the exact mechanisms by which the mammalian heart switches off this regenerative capacity after birth.