We aimed to determine the clinical features, predisposing factors, and outcome of left-sided Pseudomonas aeruginosa endocarditis in persons with no history of injection drug use. We performed a retrospective review of patient medical records from Mayo Clinic (Rochester, MN; Scottsdale, AZ; and Jacksonville, FL) for all cases of left-sided P. aeruginosa endocarditis. We identified 4 cases. We present these cases, as well as a review of the English-language medical literature. Data gathered included the year the case was reported; the valve involved; treatment, including valve replacement surgery; and outcome, if known. Left-sided P. aeruginosa endocarditis in persons without injection drug use is a rare but serious infection, with a history of instrumentation as a common predisposing condition. Valvular surgery is indicated, when possible, for the best chance of survival, along with extended therapy with combination antibiotics for complete recovery.