• We undertook a study of 414 bacteremic patients (167 with Haemophilus influenzae and 247 with Streptococcus pneumoniae bacteremia) to evaluate their clinical presentation, laboratory and clinical results, and subsequent outcomes. Patients with H influenzae bacteremia were more likely to have soft-tissue foci, poorer clinical appearance at presentation, and be at higher risk for subsequent serious focal infections, persistent bacteremia, and subsequent hospital admissions than patients with S pneumoniae. Patients with H influenzae bacteremia had a 21.1-fold increase in risk of meningitis (95% confidence interval [CI] of 3.8 to 78.0) compared with those with S pneumoniae. The odds ratio for initial lumbar puncture was 5.25(95% Cl [1.1-23.6]). Ambulatory patients treated with antibiotics at presentation were less likely to develop new serious soft-tissue infections, persistent bacteremia, or to require subsequent hospital admissions than untreated patients. The effect of treatment was greater for patients with S pneumoniae than those with H influenzae. Careful follow-up and reevaluation of patients with presumptive bacteremia is essential because treated and untreated patients can still develop serious soft-tissue infections.