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Background and Aims Effective postoperative pain management is critical for patients undergoing modified radical mastectomy (MRM). Serratus anterior plane block (SAPB) with ropivacaine provides regional analgesia, but its duration and efficacy may be enhanced with adjuvants. This study compares dexamethasone and dexmedetomidine as adjuncts to ropivacaine in SAPB for postoperative pain control in MRM patients.Methods In this prospective, randomized, double-blind clinical study, 60 female patients (ASA I-II, aged 18–65 years) undergoing MRM were enrolled after institutional approval(IHECSR/AIIMSBPL/AUG/05) and CTRI (CTRI/2024/10/075350). Patients were randomly assigned to two groups (n=30 each): Group RD (ropivacaine 0.5% 20 mL + dexamethasone 8 mg) and Group RM (ropivacaine 0.5% 20 mL + dexmedetomidine 1 µg/kg). SAPB was performed under ultrasound guidance preoperatively. The primary outcome was the duration of analgesia, defined as the time to the first analgesic request. Secondary outcomes included postoperative pain scores (Visual Analog Scale, VAS) at 2, 6, 12, and 24 hours, total analgesic consumption (tramadol), and adverse effects.Results Group RM exhibited a significantly longer duration of analgesia (18.4 ± 2.3 hours) compared to Group RD (14.7 ± 2.1 hours; p<0.001). VAS scores were lower in Group RM at 12 and 24 hours (p<0.05). Total tramadol consumption was reduced in Group RM (85.3 ± 20.1 mg) compared to Group RD (120.5 ± 25.4 mg; p<0.01). Adverse effects, including nausea and sedation, were comparable between groups, with no significant differences (p>0.05). No serious complications, such as pneumothorax or local anesthetic toxicity, were reported.Conclusions Dexmedetomidine as an adjunct to ropivacaine in SAPB provides a longer duration of analgesia, lower pain scores, and reduced analgesic consumption compared to dexamethasone in MRM patients, with a similar safety profile. Dexmedetomidine may be a superior adjuvant for enhancing SAPB efficacy.