Background:Patients with Respiratory tract infections were one of the most common infectious cases presents to the Out Patient Department of Medicine in any Health Institutions.Objective of the study: To assess the efficacy and tolerability of Azithromycin and Levofloxacin for Respiratory Tract Infections.Materials and methods:This is a prospective observational study where 100 patients attending Medicine OPD at GIMS, Kalaburagi with Respiratory Tract Infections were taken in the study.Their demographic details, clinical assessment details, prescription details and any lab investigation details (optional) were recorded in the Case Record Form (CRF). Results:In this study, 54 female participated compared to 46 male patients. More number of patients were from 18-49 years age group (n=46). On day 3, azithromycin (n=14) and Levofloxacin (n=19) had coughwhereas 22 patients had fever in azithromycin compared to levofloxacin (n=27). Azithromycin (n=32), levofloxacin (n=42) still had sore throat. On day 3, azithromycin group (n=18) and levofloxacin group (n=29) patients still had one or more symptoms (cough, fever, sore throat, running nose or breathlessness), significantly more in levofloxacin group.Conclusion: In this study, Azithromycin showed slightly better efficacy and tolerability than Levofloxacin for Respiratory Tract Infections in out-patients.