Tramadol hydrochloride (T-HCl) has demonstrated to have a local anesthetic effect similar to lidocaine hydrochloride (L-HCl) when administered locally for minor oral surgical procedures. Our study aimed to compare the anesthetic effect of T-HCl versus L-HCl in maxillary premolar extraction. The study is a split-mouth, double-blind randomized clinical trial at the Faculty of Dental Sciences, Ramaiah University of Applied Sciences, Bengaluru, India. The study sample was composed of patients referred for maxillary bicuspid extraction. Patients were excluded from the sample if, allergic to the study drugs, pregnant or lactating females, and smokers. The variable is an anesthetic drug administered for local anesthesia and it is grouped into 2 categories, T-HCl and L-HCl. A supraperiosteal infiltration of T-HCl with adrenaline on one side and L-HCl with adrenaline on the contralateral side was injected. The primary outcome variable was profound anesthesia of T-HCl, where the patient sensed the loss of sensation of touch, temperature, and pain. Secondary outcomes were onset and duration of anesthesia, intraoperative pain, postoperative analgesia, and adverse reactions, were recorded. Inferential statistics, the χ2 Test, the Mann-Whitney Test, and the Wilcoxon signed-rank test were used to compare the parameters. The level of significance was set at ≤ 0.05. A total of 40 patients were included, and 80 teeth were extracted. Profound anesthesia was achieved in all the cases. The mean subjective duration of anesthesia in the T-HCl and L-HCl groups was 130.80±20.01minutes and 111.40±14.87minutes, respectively, with a P value of .001. The mean Visual Analogue Scale (VAS) score for pain during the procedure in the T-HCl and L-HCl groups was 0.60±0.67 and 1.10±0.71, respectively, with a P value of .002. The mean Visual Analogue Scale score for pain postoperatively in the T-HCl and L-HCl groups was 0.70±0.72 and 1.40±0.67, respectively, with a P value of .001. Six patients in T-HCl required postoperative analgesia when compared to 18 patients in L-HCl (Pvalue < .003). T-HCl provides similar anesthetic outcomes in the extraction of maxillary bicuspids as L-HCl.