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Background and Objectives: In Lithuania, injecting heroin and other illicit opioids has dominated high-risk drug use since about 2000. More recently, patients have reported a high-risk use of amphetamines. Newly diagnosed HIV cases among people who inject drugs peaked in 2002 and 2009 and drug-related deaths have been on the increase. Yet research has reported a limited number of available harm-reduction programs. This study aimed to estimate the size of high-risk drug using populations in Lithuania and to apply these estimates in assessing the coverage of opioid substitution treatment (OST) and needle and syringe programs (NSP)., Methods: We used indirect prevalence estimation methods (HIV and Mortality Multiplier, Capture-Recapture, Truncated Poisson and the Multivariate Indicator Method) to obtain annual prevalence estimates of the population of high-risk opioid users (HROU) and of people who inject drugs (PWID) in Lithuania in 2015/2016. We computed the coverage of OST (the annual percentage of HROU in these programs) and NSP (the number of provided syringes per PWID per year), using the prevalence estimates and the data from drug services., Results: There were between 4854 and 12,444 HROU and between 8371 and 10,474 PWID in Lithuania in 2015/2016. In addition, we obtained a preliminary estimate of 4742-7000 high-risk amphetamine users. This constitutes around 2.5-6.5 HROU and 4.4-5.3 PWID per 1000 inhabitants aged 15-64. On average, 9.9-25.5% of HROUs were in OST and an average PWID in Lithuania obtained 19-29 syringes via NSPs during the study period., Conclusions: While the current prevalence of high-risk drug use in Lithuania is comparable to other European countries and for PWID, it is above the average; and the coverage of OST and NSP services in this population is markedly lower than in most countries of the European Union and warrants further investment., (Copyright © 2020 Elsevier Inc. All rights reserved.)