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Structurally marginalized women who use drugs experience disproportionately elevated health and social inequities that require specialized responses to mitigate risk of overdose. This study aimed to longitudinally investigate incidence and predictors of first nonfatal overdose among women sex workers who use drugs. This study provides strong longitudinal evidence from the longest-standing cohort of sex workers in North America. Nonfatal overdose in this setting is a critical public health concern. Criminalization-related barriers to harm reduction strongly predicted nonfatal overdose. Structural changes to legal and policing practices alongside gender-sensitive addiction services are urgently needed.