Pharmacies sometimes restrict access to buprenorphine-naloxone (buprenorphine) for individuals with opioid use disorder. The objective of this study was to quantify the frequency of barriers encountered by patients seeking to fill buprenorphine prescriptions from pharmacies in United States (US) counties with high opioid-related mortality. To characterize buprenorphine availability, we conducted a telephone audit ("secret shopper") study using a standardized script in two randomly selected pharmacies (one chain, one independent) in US counties reporting higher than average opioid overdose rates. Availability across pharmacy type (chain versus independent), county characteristics (rurality, region, overdose rate), and day of week were analyzed using univariate tests of categorical data. Independent predictors of buprenorphine availability were then identified using a multivariable binomial regression model. Among 921 pharmacies contacted (467 chain, 454 independent), 73 % were in urban counties and 42 % were in Southern states. Of these pharmacies, 675 (73 %) reported being able to dispense buprenorphine. There were 183 (20 %) pharmacies that indicated they would not dispense buprenorphine. Independent pharmacies (adjusted prevalence ratio [aPR], 1.59; 95 % CI 1.21-2.08) and pharmacies in Southern states (aPR 2.06; 95 % CI 1.43-2.97) were significantly more likely to restrict buprenorphine. In US counties with high overdose mortality rates, one in five pharmacies indicated they would not dispense buprenorphine. Buprenorphine access limitations were more common among independent pharmacies and those in Southern states. Pharmacy-directed interventions may be necessary to ensure timely buprenorphine access for patients with opioid use disorder. Copyright © 2021 Elsevier B.V. All rights reserved.