Abstract: The present disclosure presents systems and methods of predicting overdose risk using prescription data. One such method comprises analyzing, by a computing device, a plurality of document datasets, where the document datasets comprising prescription data for a controlled substance, hospital discharge data, socioeconomic data, and vital statistics data of a subject; predicting an overdose risk for the subject within a set period of time based on the plurality of document datasets; aggregating overdose risk predictions involving the controlled substance for a plurality of subjects within a geographic region; and/or calculating an overall overdose risk involving the controlled substance for the geographic region.