Background: The surge of methamphetamine use has been a complicating factor compounding the steeply increasing number of drug overdose deaths in the U.S. Infection from blood-borne viruses including hepatitis B virus (HBV), hepatitis C virus (HCV) and HIV, related to methamphetamine use continue to grow. This study aims to examine the risk factors associated with HBV, HCV and HIV among people who used methamphetamine. Methods: People who ever used methamphetamine were identified from five National Health and Nutrition Examination Survey (NHANES) cohorts, 2007 to 2016. The outcome was either positive or negative for blood-borne viruses as identified from laboratory tests. Weighted statistics for the combined ten years of data were calculated by multiplying the weighted variable for laboratory measurements by 0.2. We examined the association of sexual activities (sexual partners, sexual identity), drug use behaviors (poly-drug use, injection drug use, frequency of drug use, age started using methamphetamine), demographics, and socio-economic status with blood-borne viruses using bivariate and multivariable logistic regression models. Results: There were 1132 participants representing approximately 11,996,319 persons who ever used methamphetamine in the U.S. Blood-borne viruses’ positive rate was 13.0 per 100,000. Multivariable logistic regression analyses showed significant associations of blood-borne infections with age 40-49 years (vs. age 20-29 years, adjusted odds ratio 4.77, 95% CI 1.11–20.55), age 50-59 years (vs. age 20-29 years, 10.25, 2.40-43.82), living within poverty index 1-1.9 (vs. poverty index >=2, 2.55; 1.19–5.49), living below the poverty threshold (vs. poverty index >=2, 2.55; 1.11 – 5.86), having lower than high school education (vs. equal or higher than high school education, 3.13; 1.51 – 6.46), sexual identity as other than heterosexual (vs. heterosexual, 5.60; 1.72 – 18.28), using methamphetamine and heroin and cocaine (vs. using methamphetamine alone, 4.24; 1.06 – 16.92), injection drug use (vs. no injection drug use, 3.15; 1.61 – 6.16), and started using methamphetamine at age above 25 (vs. started using methamphetamine at age between 10-17, 2.09; 1.01 – 4.35). Conclusions: Among people who use methamphetamine, those who use polysubstance, or who inject substances, are in urgent need for vaccination and interventions to avoid further harm from blood-borne infections.