Findings: Of 54 619 adults, 35 477 (65%) received initial antibiotic therapy concordant with 2007 ATS/IDSA guidelines. Overall, 30-day mortality was 5.8%. Patients who received guideline-concordant therapy had lower mortality than those who did not, even after adjustment for multiple confounding variables (odds ratio [OR], 0.70 [CI, 0.63 to 0.77]). Guideline-concordant therapy was associated with lower rates of sepsis and renal failure but no difference in respiratory failure. Patients receiving guideline-concordant therapy were transitioned from parenteral to oral antibiotics an average of 0.57 days sooner and had a shorter length of stay (LOS) regardless of pneumonia severity (mean reduction, 0.66 days; P < 0.001). In univariate exploratory analyses, the risk for death correlated with the use of specific classes of antimicrobials, with reductions observed in patients receiving initial empirical therapy with second- or third-generation cephalosporins, macrolides, or fluoroquinolones. In addition, even after adjustment for pneumonia severity, antibiotic coverage with activity against Legionella species was less likely to have occurred in patients who received cefepime (OR, 0.26), carbapenems (OR, 0.31), piperacillin–tazobactam (OR, 0.33), or vancomycin (OR, 0.43), and mortality was higher in patients receiving these antibiotics.