ABSTRACT Objectives This study aimed to assess whether superior clinical outcomes can be attained through piperacillin/tazobactam (TZP)+fluoroquinolone (FQ) combination therapy for severe community-acquired pneumonia (CAP) compared to TZP monotherapy. Methods This retrospective study was conducted at a tertiary care hospital in Korea. Adult inpatients diagnosed with pneumonia within 48 hours of hospitalization were included. Severe CAP was defined as a CURB-65 score of ≥ 3 or based on the 2007 guidelines of the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) definition. Only patients who received either TZP and FQ combination or TZP as initial empirical therapy were included. Results The final analysis included 145 patients; 57.9% received combination therapy and 42.1% received monotherapy. In the combination therapy group, body mass index (20.67 ± 3.28 vs. 22.26 ± 4.80, p = 0.030) and asthma prevalence (0 vs. 8.3%, p = 0.022) were significantly higher; initial symptoms, clinical severity, and causative pathogens were not significantly different between groups. White blood cell counts (12,641.64 ± 6,544.66 vs. 12,491.67 ± 10,528.24, p = 0.008), and C-reactive protein levels (18.78 ± 11.47 vs. 26.58 ± 14.97, p < 0.001) were significantly higher in the combination therapy group. Clinical outcomes, including all-cause in-hospital mortality rate (26.2 vs. 33.3%, p = 0.358), were not significantly different between the groups. Multivariate analysis identified no significant association between FQ combination and all-cause in-hospital mortality. Conclusion In patients with severe CAP, there were no differences in the clinical outcomes, including mortality, between the TZP and FQ combination therapy and TZP monotherapy. FQ combination was not significantly associated with in-hospital mortality.