Background and Objective Males and females who use methamphetamine (MA) differ in socio-demographics, MA diagnoses, co-morbidities, and brain activity. The objective of this study was to investigate sex differences in the characteristics of MA use and dependence in patients at a Thai substance treatment center. Methods Demographic, MA use, and diagnostic data for 782 MA users were obtained by using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA), Thai version. Categorical comparisons of males (n=413, 53%) and females (n=369, 47%) were made by chi-square test. Factors significantly differentiating men and women with respect to MA dependence were identified by logistic regression analysis controlling for demographic, diagnostic, and MA use variables. Results Males admitted to residential drug treatment for MA use had an earlier age of onset for both MA use (17.7±4.1 vs. 19.7±6.2 years, t=-5.3, p<0.001) and dependence (20.4±5.2 vs. 22.2±6.4 years, t=-3.6, p<0.001). Females were more likely than males to be MA dependent (79% vs. 60%, χ21=33.7, p<0.001), and to experience MA withdrawal (65.3% vs. 48.9%, χ21=21.4, p<0.001), withdrawal related hypersomnia (77.2% vs. 64.8%, χ21=14.5, p<0.001), fatigue (77.5% vs. 70.3%, χ21=5.2, p=0.02) and psychomotor retardation (64.5% vs. 57.0%, χ21=4.5, p=0.03). Similarly, females had heavier (e.g., largest daily amount (χ21=12.4, p<0.001), more frequent (χ21 =5.1, p=0.02)) and greater lifetime episodes of MA use (χ21=24.1, p<0.001) than males. After controlling for such variables by logistic regression, being female remained a significant factor influencing the occurrence of MA dependence (OR=2.7, 95% CI=1.8-4.1, p<0.001). Shared associated factors (or comorbidities) for MA dependence in both sexes included nicotine dependence (in males; OR=4.1, 95% CI=2.4-7.0, p<0.001 and in females; OR=2.4, 95% CI=1.3-4.4, p=0.007), greater lifetime episodes of MA use (in males; OR=3.5, 95% CI=1.9-6.4, p<0.001 and in females; OR=5.9, 95% CI=3.1-11.4, p<0.001) and more frequent use (in males; OR=5.1, 95% CI=2.8-9.1, p<0.001 and in females; OR=3.6, 95% CI=1.9-6.9, p<0.001). Comorbid antisocial personality disorder predicted MA dependence in males only (OR=3.7, 95% CI=1.6-8.6, p=0.002). Conclusions The current study highlights both common (e.g., nicotine dependence and severity of MA use) and sex-specific differences (e.g., MA use/dependence characteristics and comorbidities), including sex itself, with respect to MA dependence in a Thai treatment cohort.