Neighborhood socioeconomic environment may be a determinant of injection drug use cessation. The authors used data from a prospective cohort study of Baltimore City, Maryland, injection drug users assessed between 1990 and 2006. The study examined the relation between living in a poorer neighborhood and the probability of injection cessation among active injectors, independent of individual characteristics and while respecting the temporality of potential confounders, exposure, and outcome. Participants’ residences were geocoded, and the crude, adjusted, and inverse probability of exposure weighted associations between neighborhood poverty and injection drug use cessation were estimated. Weighted models showed a strong association between neighborhood poverty and injection drug use cessation; living in a neighborhood with fewer than 10%, compared with more than 30%, of residents in poverty was associated with a 44% increased odds of not injecting in the prior 6 months (odds ratio = 1.44, 95% confidence interval: 1.14, 1.82). Results show that neighborhood environment may be an important determinant of drug injection behavior independent of individual-level characteristics.