Background: Asthma is a heterogeneous disease characterized by chronic airway inflammation and respiratory symptoms such as wheezing, shortness of breath, chest tightness and cough that vary over time and in intensity along with variable expiratory airflow limitation. The present study was conducted to compare two fixed drug combinations of vilanterol with fluticasone and salmeterol with fluticasone in tertiary care hospital. Materials & Methods: The Study was carried out on 140 patients of Asthma in the Department of Pulmonary Medicine, Guru Gobind Singh Medical College & Hospital Faridkot. Study medicines were allocated between two groups i.e. Group SF (n=70) and Group VF (n=70). Group SF was managed with inhalation therapy of Salmeterol & Fluticasone combination. Similarly, group VF was managed with inhalation therapy of the Vilanterol & Fluticasone combination. Spirometry was performed after 4 hours on 0 days. Furthermore, spirometry was performed after 7 days and 14 days of starting the treatment. RMS Helios 702 Spirometer was used for evaluation. Patients were divided equally and randomly into two groups: Group SF: - Mild and Moderate Persistent Asthma patients receiving inhalation With Salmeterol & Fluticasone Furoate. Group VF: - Mild and Moderate Persistent Asthma patients receiving inhalation with Vilanterol & Fluticasone Propionate. Results: No significant difference was observed in sex distribution in both groups (p=0.264) with 44.28% females in group SF and 40% in group VF whereas 55.72% males in group SF and 60% in group VF. It was observed that seasonal variation, allergic to dust/pollen and family history of Asthma were important risk factors for the causation of asthma in both groups. In contrast, smoking and occupational exposure seemed to be not significant as a causative risk factor for asthma. Group SF contained 81.42% of partially controlled patients and the rest had uncontrolled symptoms. Similarly, group VF had 85.71% of patients with partially controlled symptoms with the rest having uncontrolled symptoms. Both the groups were compared based upon improvement in FEV1, FEV1/FVC at 4 hours, after 7 days and after 14 days, more improvement was seen in the VF group with significant differences observed at each specified interval. Conclusion: Authors found significant improvement in the lung functions of the patient in the Vilanterol/Fluticasone group as compared to the Salmeterol/Fluticasone group. Bronchial Asthma is a chronic/heterogeneous disease warranting newer treatment for management. Novelty drugs with greater pharmacological properties with strong adherence to be studied.