The purpose of this study was to examine the impact of antimicrobial monotherapy vs combination therapy on length of stay and mortality for patients with Streptococcus pneumoniae pneumonia. Thirty-nine percent of patients received monotherapy, while 61% received combination therapy. Although there was no significant difference in mortality (OR 1.25, 95% CI = 0.25-6.8), there was a significant increase in length of stay for patients who received combination therapy (p = 0.02). Patients with bacteremic pneumococcal pneumonia treated with empiric combination therapy had no significant difference in mortality; however, they did have increased length of stay after adjusting for severity of illness. Randomized controlled trials are needed to determine what is the optimal empiric antimicrobial regime for patients with community-acquired pneumonia.