Although 2DE is considered the most sensitive method for detecting vegetations in infective endocarditis, the independent clinical significance of these vegetations continues to be debated. To further examine this, we identified 74 patients who were diagnosed as having infective endocarditis over a 54-month period. The 50 patients who underwent 2DE examination form the basis of this report. Definite vegetations were present in 21 (42%) patients and measured 1.2 +/- 0.2 cm2. The vegetation was localized to the aortic valve in 10 patients, the mitral valve in eight, and the tricuspid valve in three. A major complication, defined as death, new-onset congestive heart failure, major arterial embolus, or valve surgery occurred in 86% of the vegetative endocarditis patients compared to 62% of those without vegetations. Among those patients with vegetations, death occurred in 24%, heart failure in 38%, arterial embolus in 48%, and surgery in 43%. This compared to 7%, 21%, 21%, and 24%, respectively, in those patients without vegetations. These data support the concept that 2DE detection of a vegetation defines a high-risk subgroup of patients with infective endocarditis in whom careful monitoring and aggressive management are warranted.