Background Limited research has focused on correlates of injection drug use (IDU) among high‐risk subgroups of drug users, particularly women, who may be at increased risk for transmission of infectious diseases such as HIV and Hepatitis C. The purpose of this study is to better understand the contextual and health correlates of IDU among women living in rural Appalachia by examining (1) differences between injectors and noninjectors, and (2) the unique correlates of recent IDU and past IDU. Methods This study involved random selection, screening, and face‐to‐face interviews with 400 rural Appalachian women from jails in one state. Analyses included descriptive statistics, multinomial logistic regression, and stepwise regression to identify significant correlates of recent IDU and past IDU compared to never injecting. Results Findings indicated that 75.3% of this randomly selected sample reported lifetime injection of drugs. Contextual factors including drug use severity (RRR = 8.66, P < .001), more male sex partners (RRR = 1.01, P < .05), and having injecting partners (RRR = 7.60, P < .001) were robust correlates of recent injection practices. Conclusions This study makes an important contribution to understanding factors associated with IDU among rural Appalachian women drug users, which are strongly associated with both relational and health factors. Study findings on the specific factors associated with IDU risk have important implications for tailoring and targeting interventions that should include a focus on the relationship context reducing high‐risk injection practices.