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Background: Illicit drug use has been recognized as a major problem. Clinical studies demonstrated that poor sleep quality was associated with increased frequency of drug use and relapse. However, few studies addressed the issue of sleep quality and gender differences in illicit drug dependent subjects. The present study aimed to explore the gender differences in sleep problems in drug users. Methods: In this cross-sectional study, a total of 2,178 illicit drug users, including 1,875 male users [884 methamphetamine (MA) users and 991 heroin or other drug users] and 303 female users (78 MA users and 225 heroin or other drug users, 13.9%), from drug rehabilitation centers in Changsha, and 2,236 non-drug-using subjects, including 1,910 males and 326 females (14.6%) completed the self-report Pittsburgh Sleep Quality Index (PSQI). Results: We found that the prevalence of suggestive sleep problems (PSQI>5) between male and female was 67.4 and 75.2% in overall illicit drug use sample (p<0.001), 52.4 and 75.6% in MA users (<0.001), 80.8 and 75.1% in heroin or other drugs users (p=0.054), 26.0 and 28.8% in healthy controls (p=0.287). For sleep quality, the mean of PSQI total score (M±SD) between male and female was 7.8±4.42 and 8.9±4.15 in overall illicit drug users (p<0.001), 6.4±4.45 and 9.1±4.00 in MA users (<0.001), 9.1±3.96 and 8.9±4.21 in heroin or other drugs users (p=0.394), 4.2±2.46 and 4.4±2.51 in healthy control sample (p=0.090). These results indicated that only MA users, rather than heroin or other drugs users and healthy controls, showed gender differences in sleep problems. Conclusions: In this study, female users reported higher frequency of sleep problems and poorer sleep quality than male users in MA users' group, but not in heroin or other drug users group. Future studies aim at quantifying the benefits of treatment interventions should not neglect the influence of sleeping problems and its gender differences. [ABSTRACT FROM AUTHOR]