An investigation into whether or not the level of harm associated with injecting drug use varies depending on the drug that is injected was conducted among 151 primary heroin injectors and 145 primary amphetamine injectors. Compared to primary amphetamine injectors, primary heroin injectors were more dependent on their primary drug, had poorer social functioning, and had recently exhibited a higher degree of criminal behaviour. There were no differences between the two groups in terms of the prevalence of needle sharing, their health, or their psychological functioning, despite the amphetamine users being significantly younger and having used less frequently. It is concluded that while there are some harms that are attributable to injecting per se, the type of drug that is injected does play a mediating role in the relationship between injecting drug use and its associated harm.