Inter-appointment pain (IAP) is a subtype of postoperative pain which occurs between endodontic appointments. It may begin within a few hours after the first appointment and may continue for several days. Apart from mechanical instrumentation and thorough irrigation, intracanal medicaments play a central role in the disinfection of root canals and thus decreasing IAP. The aim of this study was to evaluate the effect of Curcuma Longa as an intracanal medicament on IAP in patients with symptomatic irreversible pulpitis (SIP). One hundred healthy adult patients having SIP in one of their single-rooted maxillary or mandibular teeth participated in this randomized, parallel, single-blinded clinical trial. After thorough biomechanical preparation, the root canals were randomly medicated with one of the following medicaments, Control (no medicament), Calcium Hydroxide, triple antibiotic paste (TAP), and Curcuma Longa. The pain was recorded using Visual analog scale at 4 h, 24 h, and every day until the seventh day. Data were analyzed using Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed-rank tests. No statistical difference in pain scores was observed between Calcium Hydroxide, TAP or Curcuma Longa groups. It can be concluded that Curcuma Longa, Calcium hydroxide, and TAP are equally effective in controlling IAP.