Aim: To compare the effect of analgesics on postoperative pain following single-visit root canal treatment in patients with symptomatic irreversible pulpitis. Materials and methods: In this randomized controlled clinical trial, 80 patients with symptomatic irreversible pulpitis of posterior teeth without any signs and symptoms of acute or chronic apical periodontitis and moderate to severe pain were divided into four groups of 20 patients each enrolled in this study. They are group I, pretreatment oral diclofenac; group II, pretreatment transdermal diclofenac; group III, posttreatment oral diclofenac; and group IV, posttreatment transdermal diclofenac. Immediately a single-visit root canal treatment is performed. The intensity of the pain was scored based on a 10-point visual analogue scores (VAS) before and after treatment for up to 24 hours postoperatively. Data were submitted for statistical analysis. Kruskal–Wallis test was performed to compare the pain scores between the four groups and the Mann–Whitney U test to test the significance between the groups. Result: At 24 hours interval postoperative after drug administration, the intensity of the pain was lower when compared to baseline values. Group IV showed significant results at 24 hours when compared to group III; no significant difference was seen between groups I and III. Conclusion: The results demonstrate that a posttreatment transdermal patch may be more effective than oral diclofenac for the management of postoperative endodontic pain.