Background <p>While various analgesic methods have been proposed in breast augmentation, limited data exist comparing their efficacy in a controlled setting. This prospective, split-body study aimed to compare the effectiveness of preoperative PECS I block and intraoperative direct local anesthetic infiltration for postoperative pain control following breast augmentation.</p> Methods <p>Twenty female patients (ASA I–II, aged 18–59) undergoing bilateral breast augmentation with identical implants via dual-plane or submuscular approaches were included. Each patient received a PECS I block on the right breast (10 mL of 0.5% bupivacaine) performed preoperatively by the same anesthesiologist. The left breast received an identical dose via direct local anesthetic infiltration administered by the same plastic surgeon prior to muscle transection. Postoperative pain was evaluated using the Numeric Rating Scale (NRS) at 30 min intervals for the first 2 h, every 2 h between 2 and 6 h, at 24 h, on postoperative day 5, and at 3 months.</p> Results <p>Pain scores were significantly lower on the PECS I block side compared to the local infiltration side during the early postoperative period (30 min to 6 h) (<i>p</i> &lt; 0.05). No significant difference was observed at 24 h, day 5, or 3 months. The mean tramadol requirement in the first 6 h was 72.0 ± 10.05 mg, with a total of 171.0 ± 21.98 mg at 24 h.</p> Conclusions <p>In this split-body study, PECS I block provided superior pain control during the early postoperative period (first 6 h) compared to direct local infiltration.</p> Level of Evidence II <p>Evidence Based Medicine Level: Evidence Level II, Therapeutic Study. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors <a href="https://www.springer.com/00266">www.springer.com/00266</a>.</p>