Introduction: One of the most important aspects of endodontic practice is to control pain during and after root canal treatment. Aim: To evaluate the effect of occlusal reduction on post-operative pain after endodontic instrumentation and obturation in patients with symptomatic irreversible pulpitis and symptomatic apical periodontitis in mandibular posterior teeth. Materials & Methods: At the first visit, before starting the treatment, participants were asked to report their pain level on the VAS. In the experimental group, after access cavity preparation, all occlusal contacts on the functional and non-functional cusps as well as on the marginal ridges were relieved from occlusion. Working length was established. Canals were then prepared by crown down technique using Revo-S Rotary instruments. After drying the canals, a cotton pellet was placed in the pulp chamber and the access cavity was closed with a temporary filling. Then, patients were asked to fill the VAS, at 6, 12, 24, 48 hours intervals. After 7 days; participants were recalled for completion of root canal treatment. temporary filling was removed using high speed handpiece, re-irrigation of root canals was done, the canals were dried using paper points and obturated by lateral condensation technique, using resin-based root canal sealer. The patients were presented with a placebo capsule for pain control, and asked to fill the VAS at 6, 12 hours intervals to register pain level. Results: The mean value for VAS scores for (no occlusal reduction) group and (occlusal reduction) group did not show a statistically significant difference at any time interval. Conclusions: Within the limitations of this study, it could be concluded that: There is no enough evidence on the effectiveness of occlusal reduction on reducing post-operative pain in mandibular posterior teeth with symptomatic irreversible pulpitis and symptomatic apical periodontitis.