Multi-phase polymer microspheres for drug encapsulation have been fabricated via solvent removal using poly( l -lactic) acid (PLLA) and poly(fumaric-co-sebacic) anhydride (20:80) (P(FA:SA) (20:80)). The process by which these spheres degrade was investigated. Characterization was conducted to determine the extent of degradation of the two polymer phases over 16 weeks using scanning-electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), gel-permeation chromatography (GPC), differential-scanning calorimetry (DSC) and nuclear magnetic resonance (NMR). These experiments showed that the P(FA:SA) (20:80) phase of the multi-phase microspheres degraded faster than the PLLA phase, leaving only some of the poly(sebacic) oligomers after 16 weeks in both the in vitro and in vivo studies. These portions could remain because they were entrapped in the PLLA phase, preventing more rapid degradation. The PLLA phase showed minimal changes over the 16 week period; there was no significant change in crystallinity and only a small decrease in molecular weight in both the in vitro and in vivo studies. The in vitro study showed a rapid mass loss initially (first 3 days), followed by a fairly constant mass through 16 weeks, while the in vivo study showed a mass gain due to tissue influx.