BackgroundCarpal tunnel syndrome (CTS) is the most common entrapment mononeuropathy. Menopausal status and/or estrogen level may play a role in CTS. The evidence regarding the association between hormone replacement therapy (HRT) in postmenopausal women and CTS is still conflicting. This meta-analysis aimed to investigate the association between carpal tunnel syndrome (CTS) and women using hormone replacement therapy (HRT).MethodsA search was conducted in the PubMed/Medline, Scopus, Embase, and Cochrane databases, from their inception through July 2022. Studies which reported on the association between any type of HRT use and the risk of developing CTS in postmenopausal women compared to a control group were included. Studies which did not include a control group were excluded. Of the 1573 articles extracted from database searches, seven studies involving 270,764 women were included of which 10,746 had CTS. The association between CTS and HRT use was evaluated using the pooled odds ratio (OR) with a 95% confidence interval (CI) under random-effects modelling. Risk of bias in each study was assessed using the Newcastle–Ottawa Scale (NOS) and version 2 of the Cochrane tool for assessing risk of bias in randomized trials (RoB 2).ResultsHRT use showed no statistically significant association with a higher risk of CTS with pooled odds ratio (OR) 1.49, 95% confidence interval (CI) 0.99–2.23, andp= 0.06, although high heterogeneity among the studies was observed (I297.0%,Q-testp-value < 0.001). Subgroup analysis of groups in non-randomized controlled studies showed a significantly increased risk of CTS, while groups in randomized controlled studies showed a decreased risk of CTS (pooled OR 1.87, 95% CI 1.24–2.83 versus pooled OR 0.79, 95% CI 0.69–0.92, respectively) with thep-value of group difference < 0.001. The risk of bias in most of the included studies was estimated to be low.ConclusionsThis meta-analysis supports the safety of using HRT in postmenopausal women with potential risk factors for CTS.Level of evidenceI, Prognosis.Registration: INPLASY (202280018).Supplementary InformationThe online version contains supplementary material available at 10.1186/s10195-023-00707-5.