We conducted a population-based study to examine the association between clinical and Doppler echocardiographic characteristics and physicians' recommendation for endocarditis prophylaxis. Of 127 consecutive Olmsted County, Minnesota, residents with newly documented isolated mitral valve prolapse, endocarditis prophylaxis was recommended three to four times more often in patients under 40 years compared with those more than 60 years of age. Using multiple logistic regression, for every 10-year increment in age, there was a 30% independent reduction in recommendations for endocarditis prophylaxis. Doppler evidence of mitral regurgitation was also independently associated with recommendations for endocarditis prophylaxis. Observations from physical examination, including systolic murmur and systolic click, were weakly associated with endocarditis prophylaxis recommendations. Mitral valve appearance (thickened vs not) was not associated with endocarditis prophylaxis. Although current recommendations for endocarditis prophylaxis and mitral valve prolapse do not address age and Doppler-detected mitral regurgitation, these variables are strongly associated with clinical decisions. Prospective, longitudinal, population-based studies are needed to define endocarditis risk further in subgroups with mitral valve prolapse to provide a more scientific basis for clinical decision making.