Background: Intracranial haemorrhage (ICH) is a serious and potentially fatal complication of oral anticoagulant therapy (OAT). Prothrombin complex concentrates (PCCs) produce a rapid and effective reversal of OAT effects, but little evidence exists on their efficacy and safety in the management of ICH in patients on OAT. Aim: To evaluate the efficacy and safety of PCCs for the rapid reversal of OAT in patients with ICH. Methods: Patients suffering from acute ICH while receiving OAT were eligible for this prospective cohort study if their international normalized ratio (INR) was ≥2.0. Stratified 35–50 IU kg–1 PCC doses were infused based on initial INR. Results: A total of 92 patients (50 males; mean age 74 years, range 34–92 years) were included. The median INR at presentation was 3.3 (range 2–9). At 30 min after PCC administration the median INR was 1.4 (range 0.9–3.1), declining to ≤1.5 in 75% of patients. The benefit of PCC was maintained for a long time, since in 98% of all post-infusion time points through 96 h the median INR remained ≤1.5 (median 1.19; range 0.9–2.3). During hospitalization neither thrombotic complications nor significant adverse events were observed and 11 patients died (11.9%). None of the deaths was judged to be related to PCC administration. Conclusions: PCC administration is an effective, rapid and safe treatment for the urgent reversal of OAT in patients with ICH. Broader use of PCC in this clinical setting appears to be appropriate.