This prospective study compared the effectiveness of nine medications and a placebo in controlling pain following obturation. A total of 588 patients who required root canal obturation were included. After obturation of root canals, each patient took one of the medications, salicylic acid (2 x 250 mg), acetaminophen (2 x 250 mg), ibuprofen (2 x 250 mg), ketoprofen (2 x 250 mg), acetaminophen (2 x 250 mg) plus codeine (2 x 250 mg), penicillin (2 x 250 mg), erythromycin base (2 x 250 mg), penicillin plus ibuprofen (2 x 250 mg), methylprednisolone (2 x 250 mg) plus penicillin (2 x 250 mg), or a placebo, every 6 h for 72 h. All medications were encapsulated in identical capsules. The patients registered their degree of discomfort on a visual analogue scale of 0 to 9. Statistical analysis of the data showed that the incidence of postoperative pain after obturation is lower than that following complete cleaning and shaping (5.83% versus 21.76%). In addition, there was no significant difference between the effectiveness of the various medications and placebo tablets in controlling postoperative pain following obturation.