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Recent increases in high-risk substance use (HRSU) (i.e., injection drug use, heroin, methamphetamine, crack/cocaine) have coincided with rising primary and secondary (PS) syphilis rates. To further understand these trends, we examined sexual risk behaviors among women, men who have sex with women only (MSW) and men who have sex with men (MSM) who were diagnosed with PS syphilis in 2018 and reported HRSU. Data on HRSU and sexual risk behaviors among persons with PS syphilis were drawn from syphilis case reports in 2018 fr