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Aim: To compare the success of an inferior alveolar nerve block (IANB) after injecting a combination of mepivacaine and tramadol or mepivacaine alone in patients with symptomatic irreversible pulpitis (SIP) in mandibular permanent molars., Methodology: This study was a double-blind, randomized, controlled clinical trial. Two study groups were selected, each consisting of 28 patients who exhibited SIP on the first or second mandibular molars. All included patients presented with moderate-to-severe preoperative pain according to the modified Heft-Parker visual analogue scale (VAS). Patients were anaesthetized using the IANB technique employing identical cartridges that contained either 1.3 mL of 2% mepivacaine with epinephrine 1 : 100 000 plus 0.5 mL of tramadol 50 mg mL(-1) (experimental group) or 1.8 mL of 2% mepivacaine with epinephrine 1 : 100 000 (control group). After 15 min, anaesthesia was evaluated by a progressive four-test examination, that is numbness of the lip, positive or negative cold test, asymptomatic management of dental hard tissues and access to dental pulp. Success of the IANB was defined as the absence of pain during any of these evaluations. The data were analysed with a chi-square, Fisher's or Mann-Whitney U test., Results: A total of 74 patients were initially assessed, with 56 patients eventually included and 18 excluded. No significant differences in age (P = 0.384) or gender (P = 1) were found between the two groups. The success rates of anaesthesia with the IANB for the experimental and control groups were 57.1 and 46.4%, respectively. The success rate of anaesthesia in the experimental group was not significantly different (P ˃ 0.05) from that of the control group. The duration of the anaesthetic effect was significantly longer for the experimental group (P = 0.026)., Conclusion: The combination of mepivacaine-tramadol achieved similar success rates for IANB when compared to mepivacaine 2% epinephrine 1 : 100 000. There was no significant difference in the anaesthetic efficacy between the control and experimental solutions, and none of the solutions tested were completely successful., (© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.)