Objectives: Palatal infiltration is the most painful and uncomfortable anesthesia technique for maxillary impacted third molar surgery (MITMS). This approach could cause patients distress and aversion to dental treatment. The aim of this study was to evaluate the anesthetic efficacy of a buccal infiltration injection without a palatal injection in MITMS. Materials and Methods: This prospective research study was a crossover split mouth-randomized controlled trial. Twenty-eight healthy symmetrical bilateral MITMS patients (mean age, 23 years) were randomly assigned to two groups. Buccal infiltration injections without palatal injections were designated as the study group and the buccal with palatal infiltration cases were the control group, using 4% articaine and 1:100,000 epinephrine. The operation started after 10 minutes of infiltration. Pain assessment was done using a visual analogue scale and a numeric rating scale after each injection and extraction procedure. Similarly, the success rate, hemodynamic parameters, and additional requested local anesthetic were assessed. Results: The results showed that the pain associated with local anesthetic injections between both groups were significantly different. However, the success rates between the groups were not significantly different. Postoperative pain was not significant between both groups and a few patients requested an additional local anesthetic, but the results were not statistically significant. For hemodynamic parameters, there was a significant difference in systolic pressure during incision, bone removal, and tooth elevation. In comparison, during the incision stage there was a significant difference in diastolic pressure; however, other steps in the intervention were not significantly different between groups. Conclusion We concluded that buccal infiltration injection without palatal injection can be an alternative technique instead of the conventional injection for MITMS.