Electron paramagnetic resonance (EPR) imaging was applied to investigate further the in vitro degradation process of poly(ortho esters) containing 30 mol % lactic acid units in the polymer backbone (POE[70]LA[30]) and developed for controlled drug delivery. The objective of this study was the direct and continuous determination of pH values inside the degrading POE[70]LA[30]. pH-sensitive nitroxide spin probes 4-amino-2,2,5,5-tetramethyl-3-imidazoline-1-yloxy, 2,2,3,4,5,5-hexamethylimidazolidine-1-yloxy, and 2,2,4,5,5-pentamethyl-3-imidazoline-1-yloxy were calibrated in buffer solutions in order to cover a pH range between 1.0 and 8.0. Nitroxide spin probes were incorporated in POE[70]LA[30], and polymer samples were incubated in 0.1 M phosphate buffer (pH 7.4) at 37 °C. At selected times, polymer samples were removed for the determination of pH values inside the eroding POE[70]LA[30] by EPR at a frequency of 9.4 GHz. EPR imaging showed that the in vitro degradation of POE[70]LA[30] followed a two-phase process: in the first week of incubation, diffusion of water, and in consequence polymer degradation, were limited to the surface of the hydrophobic POE[70]LA[30] where pH values between 6.0 and 7.4 were measured. After 1 week of incubation, water diffused into the core of the sample, allowing the determination of pH values inside the eroding POE[70]LA[30] until complete erosion. Results indicated the formation of a pH gradient, with the most acidic environment inside the eroding sample where the lowest pH value of 3.8 was measured and higher pH at the surface. It was also possible to observe a polymer erosion front moving down within the polymer matrix in the course of time. The pH value of 3.8 measured inside the degrading POE[70]LA[30] remained constant until polymer samples disintegrated at day 23, where no EPR signal was detectable. In conclusion, EPR imaging allows the noninvasive spatially resolved observation of pH changes within POE[70]LA[30], and results confirmed that the in vitro erosion mechanism of POE[70]LA[30] was neither bulk erosion nor pure surface erosion.