Aim: The purpose of this randomized clinical trial was to assess postoperative pain incidence and intensity in patients with non-vital pulp and symptomatic apical periodontitis (SAP) after intracanal dressing with 0.2% cetrimide gel compared to calcium hydroxide paste. Methods: Forty-six patients having mandibular posterior teeth diagnosed with non-vital pulp and SAP received conventional endodontic treatment in two visits. In the first visit, canals were prepared using ProTaper Universal rotary instruments along with 2.5% NaOCl irrigating solution. Participants were then divided into two groups according to the applied intracanal medication, either 0.2% cetrimide gel (CTR group) or calcium hydroxide paste (CH group). Postoperative pain was assessed on a numerical rating scale (NRS) at 4, 24, 48, and 72 hours and 4, 5, 6, and 7 days. The pain intensity was assigned into four categorical scores: 1, no pain (score 0); 2, mild (scores 1-3); 3, moderate (scores 4-6); 4, severe (scores 7-10). Obturation was performed in the second visit. Participants recorded the intake of placebo capsule which was given to them, analgesic intake and when flare up occurred. Data were analyzed using Mann-Whitney, chi square and Fisher exact tests. Results: Regarding postoperative pain intensity, the median value for the NRS scores was the same for both CTR and CH groups [(3) at 4 hours and (zero) for the rest of time points] with no statistically significant difference between them. In addition, no statistically significant difference was shown in postoperative pain incidence for the different pain categories at any of the recorded time points. For the incidence of medication intake and flare up no statistically significant difference was found between the two groups (P > 0.05). Conclusion: Both 0.2% CTR gel and CH paste showed comparable postoperative pain incidence and intensity as well as medication intake and flare up incidence.