We constructed a prototype positron emission tomography (PET) system and experimentally evaluated large-volume 3-D cadmium zinc telluride (CZT) detectors for potential use in Compton-enhanced PET imaging. The CZT spectrometer offers sub-0.5 mm spatial resolution, an ultrahigh energy resolution (~1% @ 511 keV) and the capability of detecting multiple gamma-ray interactions that simultaneously occurred. The system consists of four CZT detector panels with a detection area of around 4.4 cm × 4.4 cm. The distance between the front surfaces of the two opposite CZT detector panels is ~80 mm. This system allows us to detect coincident annihilation photons and Compton interactions inside the detectors and then exploit Compton kinematics to predict the first Compton interaction site and reject chance coincidences. We have developed a numerical integration technique to model the near-field Compton response that incorporates Doppler broadening, detector's finite resolutions, and the distance between the first and second interactions. This method was used to effectively reject random and scattered coincidence events. In the preliminary imaging studies, we have used point-sources, line-sources, a custom-designed resolution phantom and a commercial image quality (IQ) phantom to demonstrate an imaging resolution of approximately 0.75 mm in PET images, and Compton-based enhancement.