Seven hundred fifty-two individuals (57% female, 96% white, and 90% aged ≥ 40 years) representing 53 zip codes in Appalachia donated 16 956 containers (eg, vials, bottles) of medications intended for use by 1210 patients. No donors refused to participate in the study. When given the opportunity to indicate 1 or more reasons for donating medicines at take-back events, donors indicated a desire to clean out their medicine cabinets (68%), environmental concerns associated with disposing of medicines with other waste (45%), and accidental poisoning concerns (14%) as motivating factors. A total of 1128 containers of controlled substances were donated, which represented 9.3% of all prescription medications. The Figure shows the composition of doses of controlled substances obtained from 402 donors at 6 take-back events. A total of 11 406 controlled substance dose units were donated. Hydrocodone combinations, oxycodone and oxycodone combinations, and methadone, 3 commonly prescribed OPRs, accounted for 32%, 11%, and 5% of total donated controlled substance doses, respectively. The mean (SD) number of dose units per donor for hydrocodone-, oxycodone-, andmethadone-containing medications was 24.4 (23.4), 20.5 (19.9), and 79.4 (46.9) U, respectively. A total of 54% and 86% of donors lived within a 10- and 20-mile radius of the nearest donation location, respectively.