Relationships between molecular structure and the degradation mechanism of degradable polymers are of special interest for temporary medical applications. The in vitro degradation study of three aliphatic polymers-poly(trimethylene carbonate) (PTMC), poly(trimethylene carbonate-co-caprolactone) (PTMC-PCL), and poly(adipic anhydride) (PAA)-revealed that these polymers exhibit degradation times from several years (PTMC) to 1 day (PAA). PTMC degraded unexpectedly slow, accompanied by very small changes in weight loss, molecular weight (SEC), and in morphology (DSC, SEM). The degradation was independent of initial molecular weight, ionic strength of the water solution, temperature, and shaking motions. The copolymer PTMC-PCL showed a higher degradation rate compared to PTMC, with preferential degradation of amorphous parts leading to an increase in % crystallinity. The surprisingly rapid degradation of PAA showed characteristics typical for a surface-like eroding system in contrast to PTMC and PTMC-PCL. The degradation products corresponded to the repeating unit of the polymers. The hydrolysis rate increases in the order carbonate, ester, anhydride, and by combining different molecular structures we achieve specific degradation behavior. A change in hydrolysis rate of the labile bond is predicted by altering the electronegativity of groups near the carbonyl-oxygen region.