The leading cause of death in the United States is cardiovascular disease. The majority of these cases result from heart failure post-myocardial infarction (MI). We present data providing evidence for use of acetalated dextran (AcDex) microparticles as a delivery vehicle for therapeutics to the heart post-MI. We harnessed the tunable degradation and acid-sensitivity of AcDex in the design of microparticles for intramyocardial injection. The particles released a model protein, myoglobin, and a sensitive growth factor, basic fibroblast growth factor (bFGF), over a wide range of time frames (from days to weeks) based on the percentage of cyclic acetals in the AcDex, which was easily controlled with acetalation reaction time. The release was shown in low pH environments, similar to what is found in an infarcted heart. bFGF maintained activity after release from the microparticles. Finally, biocompatibility of the microparticles was assessed.