Polyglycolide (PGA) materials have been widely used in the medical field, but the degradation mechanism in the natural environment is still unclear. High-viscosity PGA was prepared by using twin-screw reaction extrusion polymerization. The mass and intrinsic viscosity of PGA samples, the pH of the solution surrounding the PGA samples in water, and the number of degradation products resulting from the degradation of the PGA samples were studied under different conditions and at different temperatures. PGA does not degrade at 70 °C in either dry air or in a vacuum. Infrared spectroscopy (FTIR) and differential spectroscopy revealed that the PGA samples in water at 70 °C for 40 days had a substantially reduced mass and substantially altered thermal behavior when compared with the control sample (undegraded PGA sample). The degradation of the PGA samples in humid conditions at 70 °C was similar to the degradation of the samples in water at 70 °C. The results of this study indicate that water and water vapor (moisture) in the natural environment are the main causes of PGA degradation, and higher temperatures accelerate the degradation process, which shortens the shelf life and life of PGA.