Background: Postoperative pain following open cholecystectomy is frequently severe due to the wide subcostal incision, requiring effective pain management strategies such as the Transversus Abdominis Plane (TAP) block. The addition of analgesic adjuvants, including dexmedetomidine and fentanyl, may enhance the quality of TAP block analgesia; however, their relative effectiveness remains inconsistent. Methods: This randomized double-blind clinical trial included patients undergoing open cholecystectomy who received a subcostal TAP block. Participants were randomly assigned to two groups: ropivacaine 0.5% combined with dexmedetomidine 1 μg/kg (Group D) or ropivacaine 0.5% combined with fentanyl 1 μg/kg (Group F). Pain intensity was evaluated using the Numeric Rating Scale (NRS) at rest and during mobilization at 2, 8, 12, and 24 hours postoperatively. Secondary outcomes included duration of analgesia, total rescue analgesic consumption, and the incidence of adverse effects within the first 24 hours. Results: No significant differences in NRS scores were observed between the groups at all time points (p > 0.05). Group D demonstrated a significantly longer duration of analgesia compared with Group F (8.8 ± 0.8 hours vs 7.4 ± 0.6 hours; p < 0.05). Total rescue analgesic consumption and the incidence of postoperative nausea and vomiting were also significantly lower in Group D (p < 0.05). No hypotension or bradycardia was reported in either group. Conclusion: Dexmedetomidine is superior to fentanyl as an adjuvant to ropivacaine in subcostal TAP block, providing longer analgesia, reduced opioid requirements, and a lower incidence of postoperative nausea and vomiting.