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Introduction Effective management of postoperative pain is essential for enhancing recovery and improving patient satisfaction after breast surgery. Traditionally, bupivacaine, a long-acting local anaesthetic, has been widely employed for this purpose. More recently, liposomal bupivacaine, a novel prolonged-release formulation, has been introduced as a potential alternative. Although several randomised controlled trials (RCTs) have evaluated these agents, their comparative efficacy remains uncertain. This protocol describes the methodology for a systematic review and meta-analysis designed to assess the analgesic effectiveness of conventional bupivacaine versus liposomal bupivacaine in the setting of breast surgery.Method and analysis This study is designed as a systematic review and meta-analysis. A comprehensive literature search will be conducted in PubMed, Web of Science, Embase via Ovid, Medline via Ovid and the Cochrane Central Register of Controlled Trials to identify eligible RCTs up to the present date. The search strategy will combine relevant keywords and Medical Subject Headings terms related to bupivacaine, liposomal bupivacaine, breast surgery and pain management. Eligible studies will include RCTs enrolling adult patients (≥18 years) undergoing breast surgery. The interventions of interest are liposomal versus standard bupivacaine, typically administered perioperatively—most commonly intraoperatively via local infiltration or regional block—within the context of surgery under general anaesthesia. The primary outcome is the intensity of postoperative pain within 72 hours. Two reviewers will independently screen studies, extract data and assess risk of bias using the Cochrane Collaboration’s tool. Data will be synthesised using either a random-effects or fixed-effects model, with effect sizes reported as mean differences with 95% CIs for continuous outcomes, and risk ratios for dichotomous outcomes. Subgroup analysis, sensitivity analysis and assessment of publication bias will also be performed to ensure the robustness of findings.Ethics and dissemination Ethical approval is not required as only published data will be analysed. The meta-analysis findings will be published in a peer-reviewed journal and presented at relevant scientific conferences.PROSPERO registration number CRD42023451411.