The formulation of salicylate-based poly(anhydride-ester) (PAE) microspheres was optimized by altering polymer concentration and homogenization speed to improve the overall morphology. The microspheres were prepared using three salicylate-based PAEs with different chemical compositions comprised of either a heteroatomic, linear aliphatic, or branched aliphatic moiety. These PAEs broadened the range of complete salicylic acid release to now include days, weeks, and months. The molecular weight (M w ), polydispersity index (PDI) and glass transition temperature (T g) of the formulated polymers were compared to the unformulated polymers. In general, the M w and PDI exhibited decreased and increased values, respectively, after formulation, whereas the T g changes did not follow a specific trend. Microsphere size and morphology were determined using scanning electron microscopy. These microspheres exhibited smooth surfaces, no aggregation, and size distributions ranging from 2 to 34 μm in diameter. In vitro release studies of the chemically incorporated salicylic acid displayed widely tunable release profiles.