Claims-based adherence metrics, previously significant due to their inclusion in Medicare Star Ratings, have recently become important for the non-elderly population. Commercial insurers, pharmacy benefit mangers (PBMs), and pharmacies now utilize these metrics in accreditation and performance-based incentive programs. The validity of adherence calculations, however, may be biased due to unadjudicated cash-only prescriptions. The objective of this study was evaluate the effect that cash-only prescriptions have on misclassifying commercially-insured patients as nonadherent in patients taking antidiabetic, renin-angiotensin system antagonist (RASA), or stain medications. The Medical Expenditure Panel Survey 2010-2014 was used for this study. Proportion of days covered (PDC) was calculated for all prescriptions, as well as noncash-only prescriptions, following methods outlined by the Pharmacy Quality Alliance. Adherence was defined as PDC ≥80%. Index date was the first noncash prescription fill date or the round-start-date of the first noncash prescription. Patients were included if they had ≥2 noncash claims, continuous insurance coverage, and were age 18-64. Patients with multiple insurance types, with a measurement period <91 days, with end-stage renal disease, and diabetic patients with any insulin claim, were excluded. Of patients taking a statin (N=26,458,061) the proportion considered adherent decreased from 62.1% when using all prescriptions to 51.9% when measured using noncash-only claims. For those on RASA therapy (N=20,491,429), the proportion considered adherent decreased from 62.7% to 52.5%. For patients taking antidiabetics (N=7,355,809) the proportion considered adherent decreased from 67.6% to 52.0%. On average, 1.2 million commercially-insured patients per year were misclassified nonadherent when excluding cash-only claims prior to adherence calculation. Cash-only prescriptions represent a significant source of drug-exposure misclassification bias for claims-based adherence calculations in commercially-insured patients. Commercial insurers, PBMs, and pharmacies should take steps to ensure adjudication of cash-only prescriptions to increase the accuracy of adherence metric calculation for patients taking statin, RASA, or antidiabetic medications.