ObjectivesMany studies suggest that infective endocarditis (IE) in people who inject drugs is predominantly right sided, while other studies suggest left sided disease; few have differentiated by class of drug used. We hypothesised that based on differing physiological mechanisms, opioids but not stimulants would be associated with right sided IE.MethodsA retrospective case series of 290 adult (age ≥18) patients with self-reported recent injection drug use, admitted for a first episode of IE to one of three hospitals in London Ontario between April 2007 and March 2018, stratified patients by drug class used (opioid, stimulant or both), and by site of endocarditis. Other outcomes captured included demographics, causative organisms, cardiac and non-cardiac complications, referral to addiction services, medical versus surgical management, and survival.ResultsOf those who injected only opioids, 47/71 (69%) developed right-sided IE, 17/71 (25%) developed left-sided IE and 4/71 (6%) had bilateral IE. Of those who injected only stimulants, 11/24 (46%) developed right-sided IE, 11/24 (46%) developed left-sided IE and 2/24 (8%) had bilateral IE. Relative to opioid-only users, stimulant-only users were 1.75 (95% CI 1.05 to 2.93; p=0.031) times more likely to have a left or bilateral IE versus right IE.ConclusionsWhile injection use of opioids is associated with a strong predisposition to right-sided IE, stimulants differ in producing a balanced ratio of right and left-sided disease. As the epidemic of crystal methamphetamine injection continues unabated, the rate of left-sided disease, with its attendant higher morbidity and mortality, may also grow.