IMPORTANCE: In an effort to reduce wide-scale abuse of the proprietary oxycodone hydrochloride formulation OxyContin, an abuse-deterrent formulation (ADF) was introduced in 2010. Although the reformulation produced an immediate drop in abuse rates, a definite ceiling effect appeared over time, beyond which no further decrease was seen. OBJECTIVE: To examine the factors that led to the initial steep decline in OxyContin abuse and the substantial levels of residual abuse that have remained relatively stable since 2012. DESIGN, SETTING, AND PARTICIPANTS: We used data from the ongoing Survey of Key Informants' Patients program, part of the Researched Abuse, Diversion and Addiction-Related Surveillance system that collects and analyzes postmarketing data on misuse and diversion of prescription opioid analgesics and heroin. For our survey study, patients with a DSM-V diagnosis of opioid use disorder and primary drug of abuse consisting of a prescription opioid or heroin (N = 10 784) at entry to 1 of 150 drug treatment programs in 48 states completed an anonymous structured survey of opioid abuse patterns (surveys completed from January 1, 2009, through June 30, 2014). A subset of these patients (n = 244) was interviewed to add context and expand on the structured survey. MAIN OUTCOMES AND MEASURES: In addition to key demographic measures, past-month abuse of opioids was the primary measure in the structured surveys. In the interviews, the effect of the introduction of the ADF on drug-seeking behavior was examined. RESULTS: Reformulated OxyContin was associated with a significant reduction of past-month abuse after its introduction (45.1% [95%CI, 41.2%-49.1%] in January to June 2009 to 26.0% [95%CI, 23.6%-28.4%] in July to December 2012; P < .001; χ2 = 230.83), apparently owing to a migration to other opioids, particularly heroin. However, this reduction leveled off, such that 25%to 30% of the sample persisted in endorsing past-month abuse from 2012 to 2014 (at study end [January to June 2014], 26.7%[95%CI, 23.7%-29.6%]). Among the 88 participants who indicated experience using pre-ADF and ADF OxyContin, this residual level of abuse reflects the following 3 phenomena: (1) a transition from nonoral routes of administration to oral use (38 participants [43%]); (2) successful efforts to defeat the ADF mechanism leading to a continuation of inhaled or injected use (30 participants [34%]); and (3) exclusive use of the oral route independent of formulation type (20 participants [23%]). CONCLUSIONS AND RELEVANCE: Abuse-deterrent formulations can have the intended purpose of curtailing abuse, but the extent of their effectiveness has clear limits, resulting in a significant level of residual abuse. Consequently, although drug abuse policy should focus on limiting supplies of prescription analgesics for abuse, including ADF technology, efforts to reduce supply alone will not mitigate the opioid abuse problem in this country.