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The National Treatment Outcome Research Study is the first prospective, multisite treatment outcome investigation of drug users in the United Kingdom. The findings of this influential national study are being used by the Department of Health to formulate purchasing guidance. This article presents data on substance use problems for clients (N = 1,075) in specialist inpatient, rehabilitation, methadone maintenance, and methadone reduction modalities. The most frequent problem was heroin addiction with associated polydrug use problems. There were differences between modalities in substance use at intake. Clients in residential modalities were older, were more likely to use cocaine and alcohol in addition to opiates, had longer drug careers, and had more previous treatment contact. Substantial improvements in a range of substance use problems were observed at 6-month follow-up among clients in all treatment modalities.