Background: Injection drug users (IDUs) are at high-risk for acquiring human immunodeficiency virus, hepatitis C virus, and other infections, and delaying the switch from non-injection drug use to injection to drug use could reduce the spread of these infections. Objectives: To estimate the incidence of switching from non-injected heroin use (usually smoking or "chasing") to injection and to investigate the risk factors for this change. Methods: We reviewed the socio-demographic and clinical data of 7305 heroin-dependent patients treated at a detoxification clinic of a university-affiliated psychiatric hospital in China from January 2000 to February 2009. Results: Within 1 year, the majority of non-injection drug users (NIDUs) transitioned to IDUs (59.4% within 6 months and 76.7% within 12 months). Multiple logistic regression analysis showed that marital status, years of education, employment status, age at onset of heroin use, duration of drug abuse, and initial dose were associated with the switch from NIDU to IDU. Being married (B = -0.410, OR = 0.664), being employed (B = -0.243, OR = 0.784), and older age at onset (B = -0.040, OR = 0.961) were protective factors. More education (B = 0.120, OR = 1.128), longer duration of drug abuse (B = 0.010, OR = 1.010), and a higher dose at initial drug use (B = 0.234, OR = 1.264) were risk factors. Conclusions/Importance: The study has identified several risk factors for the switch to injection among heroin users. Understanding these factors can help design new approaches to more specifically target high-risk populations and high-risk behaviors to delay or prevent the transition to injection.