Introduction.The inferior alveolar nerve block (IANB) is the most common anesthetic technique used on mandibular teeth during root canal treatment. Its success in the presence of preoperative inflammation is still controversial. The aim of this study was to evaluate the sensitivity, specificity, predictive values, and accuracy of three diagnostic tests used to predict IANB failure in symptomatic irreversible pulpitis (SIP).Methodology.A cross-sectional study was carried out on the mandibular molars of 53 patients with SIP. All patients received a single cartridge of mepivacaine 2% with 1 : 100000 epinephrine using the IANB technique. Three diagnostic clinical tests were performed to detect anesthetic failure. Anesthetic failure was defined as a positive painful response to any of the three tests. Sensitivity, specificity, predictive values, accuracy, and ROC curves were calculated and compared and significant differences were analyzed.Results.IANB failure was determined in 71.7% of the patients. The sensitivity scores for the three tests (lip numbness, the cold stimuli test, and responsiveness during endodontic access) were 0.03, 0.35, and 0.55, respectively, and the specificity score was determined as 1 for all of the tests. Clinically, none of the evaluated tests demonstrated a high enough accuracy (0.30, 0.53, and 0.68 for lip numbness, the cold stimuli test, and responsiveness during endodontic access, resp.). A comparison of the areas under the curve in the ROC analyses showed statistically significant differences between the three tests (p<0.05).Conclusion.None of the analyzed tests demonstrated a high enough accuracy to be considered a reliable diagnostic tool for the prediction of anesthetic failure.