ABSTRACT: AIMS:Examine barriers for taking glucose-lowering oral medications, associated baseline characteristics, strategies used, and the adherence impact in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. METHODS:We studied youth prescribed oral diabetes medications over two years (N?=?611, 583, and 525 at 6, 12, and 24?months). Clinicians documented barriers (e.g. forgetting, routines, other concerns) in the subsample that reported missed doses (N?=?423 [69.2%], 422 [72.4%], and 414 [78.9%] at 6, 12, and 24?months, respectively). Adherence strategies were also assessed (e.g. family, schedule, reminder device) using standard questions. Logistic regression was used to analyze associations with medication adherence. RESULTS:Those missing doses were not different from the total sample (61.5% female, 13.9?±?2.0?years, >80% racial/ethnic minorities). No baseline demographic or clinical predictors of barriers to medication adherence were identified. Among those for whom barriers were assessed, "forgetting" with no reason named (39.3%) and disruptions to mealtime, sleep, and schedule (21.9%) accounted for the largest proportion of responses. Family support was the primary adherence strategy identified by most youth (?50%), followed by pairing the medication regimen with daily routines (>40%); the latter strategy was associated with significantly higher adherence rates (p?=?0.009). CONCLUSIONS:Family supported medication adherence was common in this mid-adolescent cohort, but self-management strategies were also in evidence. Findings are similar to those reported among youth with other serious chronic diseases. Prospective studies of multi-component family support and self-management interventions for improving medication adherence are warranted. TRIAL REGISTRATION:ClinicalTrials.gov NCT00081328.