BACKGROUND: Fresh frozen plasma (FFP) is the standard treatment for severe bleeding following cardiac surgery. Despite increasing use of prothrombin complex concentrate (PCC) for coagulopathic bleeding in preference to FFP in the UK, the evidence comparing FFP versus PCC in this setting is lacking. HYPOTHESIS: In adults who develop severe bleeding, PCC is superior to FFP in reducing a composite of mortality, organ failure, or infection up to 90 days following cardiac surgery, and is more cost-effective. METHODS: Phase III pragmatic, multicentre, parallel group, superiority, non-blinded, open-label, two-stage group sequential randomised controlled trial with internal pilot embedded. Participants will be recruited by the research team at up to 20 hospitals in England and Wales. Those who have provided informed consent and who develop bleeding within 24 h of cardiac surgery (elective and urgent procedures) will be randomised to PCC (1500 IU if ≤70 kg or 2000 IU if >70 kg; a maximum of 2 doses) or FFP (4 units if ≤70 kg and 5 units if >70 kg; no maximum dose). Randomisation will be stratified by site and will allocate participants using minimisation, with a 1:1 ratio to receive PCC or FFP. Age (≥70 and <70 years) and planned type of surgery (valve only, major aortic surgery, coronary artery bypass graft + valve, and complex/combined procedure) will be the minimisation factors. The primary outcome is a composite of mortality or new onset of respiratory failure, myocardial injury, renal failure, liver injury, intestinal injury, focal neurological deficit, or infection at 90 days. Secondary outcomes will compare safety (transfusion-related reactions, thrombosis), quality of life, healthcare costs, and cost-effectiveness. A sample size of 496 participants will have a 90% power (with a 5% significance level) to detect a relative risk of 0.7 between the two groups at 90 days. The date of the 1st patient enrolled was 11th February 2025. DISCUSSION: This trial will provide evidence on the clinical/cost-effectiveness of PCC versus FFP in cardiac surgery patients who bleed post-surgery. Its outcome will provide high-quality evidence to inform the management of bleeding following cardiac surgery. TRIAL REGISTRATION: ISRCTN 92114384. Registered on 16/04/2024. ISRCTN-ISRCTN92114384: PROthrombin complex concentrate versus fresh frozen Plasma for bleeding in adults undergoing HEart SurgerY (PROPHESY-2 trial).