We know little about predictors of injection drug cessation and relapse among female sex workers who inject drugs (FSW-PWID) at the US-Mexico border. Among HIV-negative FSW-PWID taking part in a behavioral intervention study in Tijuana and Ciudad Juárez, Cox regression was used to identify predictors of time to first cessation of injection, which was defined as reporting not having injected drugs for a period of 4 months or longer, and among that subset, we examined predictors of time to injection relapse. Among 440 women, 84 (19%) reported ceasing injection during follow-up (median time to cessation = 9.3 months); of these, 30 (35%) reported relapse to injection (median time to relapse = 3.5 months). The rate of injection cessation was lower for women reporting trading sex prior to age 18 (adj. hazard ratio (HR) = 0.64, 95% confidence interval (CI) = 0.41-1.01), ever being sexually abused (adj. HR = 0.44, 95% CI = 0.27-0.71), and a higher number of vaginal sex acts with casual clients (adj. HR = 0.99 per transaction, 95% CI = 0.98-1.00). The rate of cessation was higher for women who spent more hours on the streets on a typical day (adj. HR = 1.04/h, 95% CI = 1.01-1.08) and who lived in Tijuana vs. Ciudad Juárez (adj. HR = 2.15, 95% CI = 1.14-4.07). The rate of relapse was higher among women reporting regular drug use with clients (adj. HR = 2.17, 95% CI = 0.96-4.89) and those scoring higher on a risk injection index (adj. HR = 2.04, 95% CI = 1.15-3.61). The rate of relapse was lower for FSW-PWID with higher than average incomes (adj. HR = 0.40, 95% CI = 0.18-0.89). These findings have important implications for the scale-up of methadone maintenance treatment programs (MMTPs) in Mexico and indicate a need for gender-specific programs that address sexual abuse experiences and economic vulnerabilities faced by FSW-PWID.