A detailed examination of the role of water in the hydrolysis of poly(DL-lactide/glycolide) esters is reported. The hydrolysis rate of polyester pellets was independent of moderate changes in ionic strength, pH, and buffer concentration. Total water uptake by the polymer depended on ionic strength but not pH. The hydrolysis rates were independent of the total water content of the polymer. Solid-state H-2-NMR qualitatively demonstrated the presence of two types of water ((H2O)-H-2) environments within the polymer, bulk water with free rotation and bound water with hindered rotation. Differential scanning calorimetry also showed the presence of nonfreezing water, confirming different water environments within the polymers. Quantitative solid-state 2H-NMR showed that the polymer contained a constant amount of water ((H2O)-H-2) with hindered rotation. The molar quantity of ester groups in the polymer is 25-fold higher than the molar quantity of water with hindered rotation, suggesting that water’s immobility and reactivity result from its selective hydrogen bonding to the oxygen of ester carbonyl groups. The increased hydrolysis rate, observed for polyesters with higher glycolide content, correlates with an observed increase in bound, reactive water.