Lifetime prevalence of opioid dependence is about 0.4% in western countries. Opioid-dependent patients have high morbidity and mortality and a high risk of criminal behavior. Few studies have addressed the long-term impact of opioid maintenance therapy on convictions and criminal behavior. The PREMOS study is a prospective, longitudinal, naturalistic clinical study of a nationally representative sample of 2694 opioid-dependent patients to investigate convictions and criminal behavior at baseline and after 6 years of maintenance treatment. At follow-up, 2284 patients still were eligible (84.7%). A comprehensive assessment including a patient and doctor questionnaire, and the EuropASI was completed at baseline and follow-up. Data on criminality at follow-up had been received for 1147 (70.6%) patients. A large number (84.5%) of them had been charged or convicted at any time before baseline assessment, most frequently with drug-related offenses (66.8%), acquisitive crime (49.1%), or acts of violence (22.0%). Reported charges and convictions had declined to 17.9% for the last 12 months before follow-up, which was also reflected by a significant decrease in the EuropASI subscore “legal problems” from 1.52 at baseline to 0.98 after 6 years. These data indicate a significant and clinically relevant reduction in criminal behavior in opioid-dependent patients in long-term maintenance treatment. Maintenance therapy is effective in the reduction in both narcotics-related and acquisition crime.