Acute lower respiratory tract infections (LRTI) range from acute bronchitis and acute exacerbations of chronic bronchitis to pneumonia. Among these, pneumonia represents the most frequent cause of mortality, hospitalization and medical consultation. Objective: To evaluate the safety and tolerability of fixed dose combination of Cefixime and Ofloxacin (CO2 Tablet) in the management of Respiratory tract infection a post marketing surveillance study was carried out among 215 patients of age group 18-72 years suffering from respiratory tract infection. Materials & Method: Study drug CO2 containing Cefixime 200 mg + Ofloxacin 200 mg was prescribed to be taken twice daily for a duration of 7-14 days depending upon the severity. Cough intensity, frequency of cough, fever and respiratory rate were recorded during three visit on 3rd, 7th and 14th day of treatment. Safety and efficacy was evaluated based on the global assessment by the investigator based on a three point scale marked as excellent/good/poor. Result: 93.95% patients reported fever on the first day of treatment. Body temperature was significantly reduced from baseline mean value 101 ± 0.49 °F to 99.72 ± 0.09 °F, 98.18 ± 0.142 and 97.95 ± 0.161 on 3rd, 7th and 14th day resp. Similarly the cough intensity was significantly reduced on: 3rd, 7th and 14th day from baseline. On day 3rd cough intensity was reduced by 29.4% (p<0.0001), on the day 7th cough intensity was reduced by 58.90% (p<0.0001) and on 14th day it was further reduced by 79.63% (p<0.001) from the base line. There were repeated bouts of cough at the time of diagnosis; mean ± SD value was 15.59 ± 11.65 at base line. On day 3rd, number of bouts of cough was reduced to (10.6 ± 8.7 vs. 15.5 ± 11.6) (p<0.05), on 7th day it was reduced to (5.804 ± 5.707 vs. 15.59 ± 11.65) (p<0.05) from the base line and on the 14th day of treatment it was reduced to (2.024 ± 3.751 vs. 15.59 ± 11.65) (p<0.05). On 14th day almost all the patients were devoid of bouts of cough. As per investigators assessment, 98% of patients reported good to excellent and 2% reported poor efficacy. As per investigators assessment about safety of CO2 97.9% of patient reported good to excellent and 2.1% reported poor tolerability. Rare incidences of headache and nausea were reported. No serious adverse events were reported which led to withdrawal of patients from the study. Conclusion: In conclusion this postmarketing surveillance study of fixed dose combination of cefixime and ofloxacin (CO2 Tablet) antibiotic therapy achieves a better outcome for the empirical management of respiratory tract infection with excellent efficacy, tolerability & safety in the treatment of respiratory tract infection.