Abstract Background Angiogenesis has increasingly been a target for imaging and treatment over the last decade. The integrin α_vβ₃ is highly expressed in cells during angiogenesis and are therefore a promising target for imaging. In this study, we aimed to investigate the PET tracer [⁶⁸Ga]Ga-RGD as a marker of angiogenesis following MI and its ability to predict cardiac functional parameters. Methods First, the real-time interaction between [⁶⁸Ga]Ga-RGD and integrin α_vβ₃ was investigated using surface plasmon resonance (SPR). Second, an animal study was performed to investigate the [⁶⁸Ga]Ga-RGD uptake in the infarcted area after one and four weeks following MI in a rat model (MI = 68, sham surgery = 36). Finally, the specificity of the [⁶⁸Ga]Ga-RGD tracer was evaluated ex vivo using histology, autoradiography, gamma counting and flow cytometry. Results SPR showed that [⁶⁸Ga]Ga-RGD has a high affinity for integrin α_vβ₃, forming a strong and stable binding. PET/CT showed a significantly higher uptake of [⁶⁸Ga]Ga-RGD in the infarcted area compared to sham one week (p < 0.001) and four weeks (p < 0.001) after MI. The uptake of [⁶⁸Ga]Ga-RGD after one week correlated to end diastolic volume (r = 0.74, p < 0.001) and ejection fraction (r = − 0.71, p < 0.001) after four weeks. Conclusion This study demonstrates that [⁶⁸Ga]Ga-RGD has a high affinity for integrin α_vβ₃, which enables the evaluation of angiogenesis and remodeling. The [⁶⁸Ga]Ga-RGD uptake after one week indicates that [⁶⁸Ga]Ga-RGD may be used as an early predictor of cardiac functional parameters and possible development of heart failure after MI. These encouraging data supports the clinical translation and future use in MI patients.