Background <p>Post-stroke pain (PSP) is a prevalent and debilitating complication of stroke recovery, mainly characterized by allodynia and hyperalgesia. While certain brain lesion sites, particularly thalamic lesions, have been implicated in an increased risk of PSP, evidence regarding the specific contributions of stroke injury sites to PSP development remains inconsistent. This meta-analysis aimed to synthesize available data on the relationship between stroke lesion sites and PSP incidence, providing a more detailed understanding to inform clinical management.</p> Methods <p>A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Literature searches were performed across four major databases, including Embase, Scopus, Web of Science, and PubMed, up to December 31, 2024. Studies were included if they assessed the association between stroke lesion sites and PSP and reported 95% confidence intervals (CIs) for relevant outcomes. A random-effects model was used to pool incidence estimates, and heterogeneity across studies was evaluated. Subgroup analyses were conducted based on different PSP subtypes, including post-stroke shoulder pain (PSSP) and central post-stroke pain (CPSP).</p> Results <p>From an initial pool of 14,631 screened studies, 25 met the eligibility criteria, involving a total of 3,812 stroke patients. The meta-analysis revealed a higher incidence of PSP (49% [95% CI: 0.41–0.56]) in patients with left-sided cerebral stroke compared to those with right-sided stroke. Subgroup analyses indicated significant associations between left-sided stroke lesions and both PSSP (50% [95% CI: 0.39–0.61]) and CPSP (41% [95% CI: 0.37–0.45]). Additionally, thalamic lesions were significantly associated with PSP in 36% (95% CI: 0.17–0.58) of cases. Despite some heterogeneity (I² = 96%), no significant publication bias was detected based on funnel plot analysis and Egger’s test (<i>P</i> = 0.164).</p> Conclusions <p>This meta-analysis provided significant association between left-sided cerebral stroke and the increased incidence of PSP, particularly in patients with PSSP and CPSP. Thalamic stroke was notably associated with the development of PSP. These results underscore the importance of considering stroke injury sites in the assessment and management of PSP during stroke rehabilitation. Recognizing these associations can aid in the development of targeted therapeutic strategies, ultimately improving stroke patients’ outcomes and quality of life.</p> Systematic review registration <p>PROSPERO CRD42019139928.</p>