Background: Research among people who inject drugs (PWIDs) in the USA and Mexico has identified a range of adverse health impacts associated with policing of PWIDs. We employed a mixed methods design to investigate how PWIDs from San Diego and Mexico experienced policing in Tijuana, and how these interactions affect PWIDs behavior, stratifying by country of origin. Methods: In 2012-2014,575 PWIDs in San Diego, 102 of whom had used drugs in Mexico in the past six months, were enrolled in the STAHR-II study, with qualitative interviews conducted with a subsample of 20 who had recently injected drugs in Mexico. During this period, 735 PWIDs in Tijuana were also enrolled in the El Cuete-IV study, with qualitative interviews conducted with a subsample of 20 recently stopped by police. We calculated descriptive statistics for quantitative variables and conducted thematic analysis of qualitative transcripts. Integration of these data involved comparing frequencies across cohorts and using qualitative themes to explain and explore findings. Results: Sixty-one percent of San Diego-based participants had been recently stopped by law enforcement officers (LEOs) in Mexico; 53% reported it was somewhat or very likely that they would be arrested while in Mexico because they look like a drug user. Ninety percent of Tijuana-based participants had been recently stopped by LEOs; 84% reported it was somewhat or very likely they could get arrested because they look like a drug user. Participants in both cohorts described bribery and targeting by LEOs in Mexico. However, most San Diego-based participants described compliance with bribery as a safeguard against arrest and detention, with mistreatment being rare. Tijuana-based participants described being routinely targeted by LEOs, were frequently detained, and reported instances of sexual and physical violence. Tijuana-based participants described modifying how, where, and with whom they injected drugs in response; and experienced feelings of stress, anxiety, and powerlessness. This was less common among San Diego based participants, who mostly attempted to avoid contact with LEOs in Mexico while engaging in risky injection behavior. Conclusion: Experiences of discrimination and stigma were reported by a larger proportion of PWIDs living in Mexico, suggesting that they may be subject to greater health harms related to policing practices compared with those residing in the USA. Our findings reinforce the importance of efforts to curb abuse and align policing practices with public health goals in both the US and Mexico. (C) 2016 Elsevier B.V. All rights reserved.