This study assessed correlates of inconsistent condom use with casual partners and the prevalence of sexual risk behaviors and STIs in the Mexico/Guatemala border region using a sample of 392 migrants (303 men, 85 women) who reported current substance use or problem drinking. We ran separate univariate logistic regression models for men and women, and multivariate logistic regression models for men only. Prevalence of syphilis was 1.2% among women and 2.3% among men; HIV prevalence was 2.4% among women and 1.3% among men. Inconsistent condom use with casual partners was higher in women with greater education and lower among women who sold sex. In men, less access to free condoms, drug use with sexual partners, and drug use before sex were independently associated with inconsistent condom use with casual partners. Sexual and substance use risk behaviors were common, and HIV/STI prevention efforts should target both genders and expand beyond most-at risk populations.