AbstractWhile high risk drug‐related behaviors for human immunodeficiency virus (HIV) transmission among injection drug users (IDUs) are asserted to have declined over time in response to the AIDS epidemic, evidence from longitudinal cohorts has been sparse. In a cohort of 810 IDUs (442 seronegatives and 368 seropositives) in Baltimore, we identified drug‐related risk behaviors at four consecutive semi‐annual visits. Using robust methods for repeated measurements and multiple logistic regression, we estimated the probabilities of maintaining and reducing risk behaviors according to HIV serostatus and time in the study. Seropositive participants were more likely to maintain lower risk behaviors, and behavior maintenance increased with time in study for both seronegative and seropositive IDUs. Greater risk reduction (towards non‐use and not sharing injection equipment) was seen among seropositive IDUs, with behavior change occurring soon after enrollment in the study. While behavior changes have been reported, many active IDUs, especially those still at risk for acquiring HIV infection, have not adequately reduced their risk. Continuing prevention programs and efforts in vaccine development are imperative to reduce the risk of HIV infection amo