Activation of endogenous cardiac stem/progenitor cells (eCSCs) can improve cardiac repair after acute myocardial infarction. We studied whether the in situ activation of eCSCs by insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) could be increased using a newly developed hydrogel in chronic myocardial infarction (MI). One-month post-MI pigs underwent NOGA-gu ided intramyocardial injec- tions of IGF-1/HGF (GF: both 0.5 μ g/mL, n =5) or IGF-1/HGF incorporated in UPy hydrogel (UPy-GF; both 0.5 μ g/mL, n =5). UPy hydrogel without added growth factors was administered to four control (CTRL) pigs. Left ve ntricular ejection fraction was increased in the UPy-GF and GF animals compared to CTRLs. UPy-GF delivery reduced pathological hypertrophy, led to the formation of new, small cardiomyocytes, and increased capillarization. The eCSC popula tion was increased almost four- fold in the border zone of the UPy-GF-treated hearts compared to CTRL hearts. These results show that IGF-1/HGF therapy led to an improved cardia c function in chronic MI and that effect size could be further increased by using UPy hydrogel.