In vivo release profiles of drug-loaded biodegradable implants were noninvasively monitored and characterized using X-ray computed tomography (CT). The imaging method was adapted and optimized to quantitatively examine the release of an active agent from a model cylindrical PLGA device (the millirod) into rabbit livers over 48 h. Iohexol, a CT contrast agent, served as a model drug; optimization of CT acquisition parameters yielded a sensitivity of 0.21 mg/mL (or 95 microg iodine/mL) for this agent. In vitro validation of the method was carried out by tracking release of iohexol in gelatin gel phantoms. In vivo release in rabbit livers was characterized through quantitative analysis of CT images and compared with UV-Vis analysis of the explanted devices at three implantation times. After correction for respiratory motion, CT analysis correlates well with the extracted iohexol data at all time points. The percent error between the actual and experimental image data was below 10%. This study demonstrates the potential of using computed tomography to noninvasively quantify the rate of agent release from controlled delivery devices in vivo.