Background: The present study was conducted to compare multiple and single file system in endodontics. Materials & Methods: The present study was conducted on 60 patients requiring root canal therapy. Endodontic therapy was performed with different rotary nickel-titanium (NiTi) MF systems (Group I) and Wave One SF system (Group II). Assessment of post operative pain and improvement of oral-health-related quality of life was measured. Results: In this study in group I, endodontic therapy was performed with different rotary nickel-titanium (NiTi) MF systems and in group II root canal treatment was performed using Wave One SF system. We found that mean pain VAS in group I was 42.1 and after 14 days was 10.4 and in group II was 43.5 before and 9.6 after 14 days. Intergroup comparison was non- significant (P> 0.05). The mean OHIP-G 14 score in group I was 12.6 and 3.2 before and after 14 days respectively and in group II was 13.2 and 4.7 before and after 14 days respectively. Intergroup comparison was non- significant (P> 0.05). Conclusion: Authors found that both systems were comparable in terms of pain reduction and improving oral health related quality of life. Key words: Root canal, Pain, Quality of life.