Tranexamic acid (TXA) reduces the risk of death and is recommended as a treatment for women with severe postpartum bleeding. There is hope that giving TXA shortly before or immediately after birth could prevent postpartum bleeding. Extending the use of TXA to prevent harmful postpartum bleeding could improve outcomes for millions of women; however we must carefully consider the balance of benefits and potential harms. This article describes the protocol for a systematic review and individual patient data (IPD) meta-analysis to assess the effectiveness and safety of TXA for preventing postpartum bleeding in all women giving birth, and to explore how the effects vary by underlying risk and other patient characteristics. Methods: We will search for prospectively registered, randomised controlled trials involving 500 patients or more assessing the effects of TXA in women giving birth. Two authors will extract data and assess risk of bias. IPD data will be sought from eligible trials. Primary outcomes will be life-threatening bleeding and thromboembolic events. We will use a one-stage model to analyse the data. Subgroup analyses will be conducted to explore whether the effectiveness and safety of TXA varies by underlying risk, type birth, maternal haemoglobin (Hb), and timing of TXA. This protocol is registered on PROSPERO (CRD42022345775). Conclusions: This systematic review and IPD meta-analysis will address important clinical questions about the effectiveness and safety of the use of TXA for the prevention of postpartum bleeding that cannot be answered reliably using aggregate data and will inform the decision of who to treat. PROSPERO registration: CRD42022345775 Keywords Anti-fibrinolytics; Tranexamic acid; childbirth; postpartum haemorrhage; meta-analysis.