Background: Intraoperative autonomic neural blockade (ANB) is a novel approach used to reduce pain, postoperative nausea and vomiting (PONV), and analgesic consumption following laparoscopic sleeve gastrectomy (LSG), and other procedures. This study compares the effect of ANB administration at the onset versus end of procedure. Methods: A secondary analysis was performed on a previous randomized controlled trial (RCT). Patients undergoing LSG were randomized to receive ANB either at the beginning or end of the procedure. The primary outcome was patient-reported pain scores, while secondary outcomes included PONV and analgesic consumption, evaluated 1, 8, and 24 h postoperatively. Results: Out of the 81 patients recruited in the original RCT, 37 in the onset and 35 in the end groups were analyzed. Both groups exhibited low pain scores, PONV, and analgesic consumption at any period. However, a higher percentage of patients reported no pain when ANB was administered at the end of the procedure (51% vs. 35%). Similarly, fewer patients experienced PONV when ANB was performed at the end of LSG (51% vs. 34% for nausea and 24% vs. 11% for vomiting). Conclusions: ANB safely and effectively reduces postoperative pain, PONV, and the need for analgesics, especially opioids after LSG, regardless of administration timing. Clinical Trial Registration: NCT05668845.