The objective of this study was to identify longitudinal patterns of injection drug use over 20 years in the AIDS Linked to the Intravenous Experience (ALIVE) Study, a community-based cohort of injection drug users (IDUs) in Baltimore, Maryland, with a focus on injection cessation. Starting in 1988, persons over 18 years of age with a history of injection drug use were recruited into the study. Participants provided information on their injection drug use semiannually through 2008. The analysis was restricted to 1,716 IDUs with at least 8 study visits. Finite mixture models were used to identify trajectories and predictors of injection patterns over time. The mean age of participants was 35 years; 75% were male, and 95% were African-American. Five distinct patterns were identified: 2 usage patterns (32% engaged in persistent injection and 16% had frequent relapse) and 3 cessation patterns (early cessation (19%), delayed cessation (16%), and late cessation (18%)). A history of drug treatment, no recent use of multiple substances, and less frequent injection distinguished the early cessation group from the other groups. This study demonstrated multiple trajectories of drug injection behaviors, with a substantial proportion of IDUs stopping injection over extended time frames. For maximum effectiveness, public health programs for IDUs should be long-term, comprehensive, and targeted toward individual patterns of use.