Aim: Propolis is a flavonoid-rich resinous product of honeybees. Propolis is less cytotoxic and more effective against resistant microorganisms than calcium hydroxide as well as biocompatible to the periradicular tissues. The aim of this parallel single-blinded randomized clinical trial was to evaluate propolis versus calcium hydroxide, intracanal medicaments, on post-operative pain in patients with necrotic single canal teeth. Methods: Forty-six participants, aged 20-40 years, with necrotic pulp, single-root, single canal teeth were randomized into 23 participants in each group; calcium hydroxide (control) and propolis (intervention). Root canal treatment was done in two visits and the medicament was applied for one week in between. Participants rated their pain on a numerical rating scale at 24, 48, 72 hours and at 7 days. The data was statistically analyzed by multivariate analysis and t-test. The significance level was set at P ≤ 0.05 for all tests. Results: The incidence of post-operative pain between both groups showed no statistically significant difference at different time intervals (p>0.05). There was a non-significant, gradual decrease in post-operative pain of all 46 participants in both propolis (P=0.17) and calcium hydroxide (P=0.274) groups, at different time intervals. Conclusions: The intracanal use of both calcium hydroxide and propolis were equally effective in controlling post-operative pain. Propolis can be used as an alternative intracanal medicament to calcium hydroxide paste.