The purpose of this study was to examine the prevalence and correlates of opioid analgesic injection (OAI) in a cohort of rural opioid analgesic users. Cross-sectional study of 184 participants from rural Appalachian Kentucky. The majority of participants were male (54.9%), white (98.4%) and the median age was 30 years (interquartile range: 24-37). The self-reported lifetime prevalence of injection drug use (IDU) was 44.3%, with 35.3% of respondents reporting injection of oral opioid analgesic formulations. The prevalence of self-reported hepatitis C (HCV) was 14.8%, significantly greater than those not injecting opioid analgesics (1.7%) (p<0.001). Receptive needle sharing, distributive needle sharing and sharing of other injection paraphernalia was reported by 10.5%, 26.3%, and 42.1% of those currently injecting, respectively. Opioid analgesic injection was more prevalent in this rural population than has been found in previous reports. This study suggests a rising problem with injecting among rural opioid users, a problem more typically associated with urban drug users. Educating injectors of opioid analgesics on safe needle practices is necessary in order to curb the transmission of HIV, HCV, and other infectious diseases. Further study on the longitudinal course of opioid analgesic injection in this population appears warranted.