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Background and Objectives: We compared two common antibiotic regimens for the treatment of mild to moderate CAP: levofloxacin versus β-lactam and macrolide combination; in terms of their efficacy and side effects. Materials and Methods: Patients with mild to moderate CAP were randomized into two groups. Group I received a combination of 1 gram ceftriaxone daily and 500 mg azithromycin daily for 5-7 days. Group II received levofloxacin 750 mg daily for five days. The signs and symptoms, hospitalization length, and the side effects were investigated. Results: There were 77 and 74 patients in groups I and II. The vital signs of group II were significantly better on the 3rd day of admission, except for the temperature (P=0.09). The O2 saturation of group II was markedly improved on the 5th day of admission (P=0.0061). In terms of clinical symptoms and hospitalization length, group II was considerably better. However, the rate of side effects in both groups was similar (P=0.885). Conclusion: Hospitalized patients with mild to moderate CAP might take more advantage of fluoroquinolone administration. It could improve the patients' signs and symptoms and reduce hospitalization length, compared with the combination of macrolide and cephalosporin, with the same rate of side effects.