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PWID population size estimates in the United States are based on small numbers and are likely biased by undercoverage of key populations and self-report. Novel methods as discussed in this article may improve our understanding of PWID population size and their health needs. PWID population size estimates in the United States are based on small numbers and are likely biased by undercoverage of key populations and self-report. Novel methods as discussed in this article may improve our understanding of PWID population size and their health