Injecting drug use is often associated with deep-seated infection. In Lothian in Scotland there has been a recent increase in the use of injected new psychoactive substances (NPS). Patients who have injected NPS have presented with Staphylococcus aureus bacteraemia (SAB) with life-threatening complications. We describe a unique case-series of 14 episodes of SAB in ten patients. Users of injected NPS had a significantly higher incidence of endocarditis and cavitating pulmonary lesions (P < 0·05) compared to those who inject only opiates. Cases of SAB in people who inject NPS have contributed to a significant rise in the overall incidence of SAB in people who inject drugs (P < 0·05) which has in turn impacted on the ability of Lothian to meet national targets for reducing the incidence of SAB.