Background Erector spinae plane block (ESP) is inevitably effective in posterior thoracic surgeries, but its efficacy and safety in anterior thoracic surgeries—particularly bilateral surgeries—remain in dispute. This study aimed to evaluate the analgesic efficacy of rhomboid intercostal block (RIB) and ESP after reduction mammoplasty. Methods This prospective randomized controlled study was conducted on 72 patients scheduled for reduction mammoplasty. Patients were randomly assigned to three groups. Group C received general anesthesia, and groups ESP and RIB received ESP and RIB blocks, and general anesthesia. The primary outcome was the first rescue analgesic time. Postoperative pain score, 24 h nalbuphine consumption, and dermatomal level were the secondary outcomes. Results Compared with those in the ESP and control groups, the first rescue analgesic time and 24 h nalbuphine consumption were significantly longer and lower, respectively, in the RIB group. Furthermore, the RIB group had the lowest significant pain scores within the first 6 h postoperatively. Significant sensory blocking of the anterior hemithorax from T2-T9 was accomplished by the RIB, while more dermatomal blockade of the posterior hemithorax from T2-T9 was provided by the ESP. Conclusions RIB is more effective than ESP in managing pain after reduction mammoplasty. It prolongs the duration of analgesia, reduces postoperative nalbuphine consumption and is associated with a lower incidence of complications; hence, RIB can be utilized as a promising alternative in anterior thoracic wall surgeries such as reduction mammoplasty.