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Background: General anesthesia (GA) is the conventional norm whenever major breast surgeries are thought of. However, in recent years, thoracic paravertebral block (TPVB) has emerged as a potential alternative to GA. Previously, studies have compared analgesic efficacy between TPVB administered before GA and GA alone. Aims and Objectives: we aimed to compare analgesic efficacy and safety between multi-level TPVB (MPVB) and single-level TPVB (SPVB) in modified radical mastectomy (MRM). Main objective was to assess the duration of postoperative analgesia provided by MPVB and SPVB. Materials and Methods: In this prospective, randomized, double-blind study, we compared MPVB (Group M) with SPVB (Group S) using 0.3 ml/kg of 0.5% bupivacaine with 0.5 μg/kg dexmedetomidine in 60 American Society of Anesthesiologists I and II female patients who were posted for MRM. Patients were randomly allotted into Group M (n = 30) or S (n = 30). Results: Mean time to primary rescue analgesia (RA) administration was significantly longer in Group M than Group S (736.90 min vs. 581.57 min, P < 0.001). Frequency of primary RA (Group M 1.17 vs. Group S 1.87, P < 0.001) and primary RA consumption (Group M 101.17 mg vs. Group S 166.20 mg, P < 0.001) in the first 24 h of the postoperative period was significantly less in Group M than Group S. Postoperative nausea and vomiting occurred in 3.34% (n = 1) and 6.67% (n = 2) of Group M and Group S, respectively. Conclusion: Multi-level technique of administering TPVB is a better choice for providing stand-alone intraoperative anesthesia and postoperative analgesia in patients undergoing MRM.