Pain management is one of the most important aspects of endodontic treatment. Infected root canals are the most common cause of endodontic pain. Pain may also be induced following conventional endodontic therapy and even with recently available techniques total eradication of the bacteria is almost unachievable. In the recent years, use of diode lasers has gained acceptance in the endodontic field. It was found by Pawar et al. and Bjordal et al. that the diode laser acted on pain and had an anti-inflammatory effect by decreasing PGE2, bradykinin, acetylcholine, histamine, serotonin, and substance P. In earlier studies related to lasers, the use of lasers was limited to treating dentinal hypersensitivity, for its effects on vital pulpotomy, and for evaluating postoperative pain and swelling in patient undergoing extractions of impacted 3rd molar. Lately, studies performed for evaluating post-operative endodontic pain using lasers showed varying results of significant differences between control groups and test group as well as comparable differences between the two. Therefore, it remains debatable whether laser therapy is effective in reducing post-operative pain after endodontic treatment or not. According to our literature search, we found only a few studies evaluating the use of lasers for post-operative endodontic pain reduction which were mostly for the International populations. Also, to the best of our knowledge, Biolase EpicX and Pro HS Niti Rotary systems have not been used in the investigations for the same. Therefore, this clinical study proposes to investigate the incidence of post-operative pain following chemo-mechanical preparation of single rooted teeth (using Pro HS Niti Rotary systems) having symptomatic apical periodontitis with and without laser irradiation (by Biolase EpicX) for the Indian population.