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Objectives: This study aimed to investigate the ability of the diode and Nd:YAG lasers to decrease postoperative pain/discomfort after intracanal application in vital and devital endodontic cases., Material and Methods: One hundred two patients with symptomatic irreversible pulpitis and asymptomatic necrotic pulps were selected and randomly divided into three groups. After chemomechanical preparation, Nd:YAG and diode laser was applied to first and second groups for final treatment of the root canals. In the control group, no further disinfection protocol was performed upon traditional procedures. Then all the teeth were obturated in the same appointment. Pre- and postoperative pain were recorded using the VAS at 0, 12th, 24th, 48th, and 72nd hours following the treatment Kruskal-Wallis and Dunn test., Results: VAS scores were significantly the most at 12-h period compared with other time periods after treatment for all groups. There was no significant difference among Nd:YAG laser, diode laser, and control groups in non-vital cases (p > 0.05). In vital cases, Nd:YAG laser group represented significantly fewer scores compared with diode laser and control groups at 48-h period (p < 0.05)., Conclusions: The processes involving the use of Nd:YAG and diode lasers after chemomechanical preparation was found to be equivalent in terms of postoperative pain intensity after completion of treatment in one session both in vital or non-vital cases except in vital cases in Nd:YAG group at 48 h., Clinical Relevance: Adjunct clinical use of Nd:YAG or diode lasers to traditional chemomechanical preparation did not cause any improvement or deterioration on postoperative discomfort and pain in patients with symptomatic irreversible pulpitis and asymptomatic necrotic pulps.