Mortality due to left-sided endocarditis caused by Pseudomonas aeruginosa remains high despite the therapeutic regimen of high doses of an aminoglycoside plus a beta-lactam antibiotic. In this series, left-sided pseudomonal endocarditis presented as an acute illness refractory to optimal antibiotic therapy. Complications associated with active valvular infection, such as neurologic sequelae, ring and annular abscesses, congestive heart failure, and splenic abscesses, are frequent. The overall morbidity and mortality remain high; however, outcome appears to improve with surgery. Our present data suggest that early valve replacement accompanied by a 6-week course of high doses of a combination of drugs may be the optimal therapy for left-sided pseudomonal endocarditis. This approach not only may prevent serious and potentially lethal complications of the disease but also may cure them.