Recognition of the increasing prevalence of outpatient antibiotic use prompted this review of 32 patients with verified infectious endocarditis. The results of 161 quantitative blood cultures obtained before definitive therapy were correlated with clinical information to determine whether outpatient antibiotic administration influenced blood culture positivity. In 17 patients receiving outpatient antibiotics, 56 (64%) of 88 blood cultures obtained before definitive treatment were positive, whereas all cultures obtained from 15 patients without recent antibiotic exposure were positive. Notably, seven patients showed a phase of total suppression, and two patients showed a phase of partial suppression of blood culture positivity after discontinuation of outpatient antibiotic treatment. Consequently, patients with recent antibiotic exposure and suspected endocarditis should have blood cultures obtained initially and periodically throughout the phase of potential suppression of bacteremia to optimize the chance of obtaining a positive result.