Objectives. We quantified controlled substance donations via permanent drug donation boxes over 2 years in a region with high prescription abuse, assessing medication characteristics, time between dispensing and donation, and weight of medications donated per capita. Methods. In partnership with Drug Enforcement Administration and local law enforcement, we analyzed permanent drug donation box collections in 8 Northeast Tennessee locations from June 2012 to April 2014. We recorded controlled substance dosage units along with the product dispensing date. Results. We collected 4841 pounds of pharmaceutical waste, 4.9% (238.5 pounds) of which were controlled substances, totaling 106 464 controlled substance doses. Analysis of dispensing dates for controlled substances indicated a median of 34 months lapsed from dispensing to donation (range = 1–484 months). The mean controlled substance donation rate was 1.39 pounds per 1000 residents. Communities with fewer than 10 000 residents had a statistically higher controlled substance donation rate (P = .002) compared with communities with 10 000 or more residents. Conclusions. Permanent drug donation boxes can be an effective mechanism to remove controlled substances from community settings. Rural and urban community residents should be provided convenient and timely access to drug disposal options.