The objective of the present study was to investigate the efficacy of a four-factor prothrombin complex concentrate (Prothromplex, PTX) in shortening prolonged international normalized ratio or controlling life-threatening bleeding. The study was a retrospective single-centre study that included 142 patients treated with PTX and allocated in three groups: patients on vitamin K antagonists (VKA) (acenocumarol) and undergoing invasive procedure or presenting with severe bleeding (n = 76), patients treated with VKA presenting with intracranial haemorrhage (n = 22), and patients not on VKA and presenting with uncontrolled bleeding (n = 44). The primary outcome variable was international normalized ratio (INR) return to the norm after PTX infusion. Secondary outcome variables included bleeding control and reduction of transfusion rate. Overall, patients received a median of 1200 IU (≈15 IU/kg) of PTX, and INR decreased from 4 ± 3 to 1.7 ± 1.2 (P < 0.01) in all groups, although it remained at least 1.4 in 38% of patients (29.3% among patients receiving 25 IU/kg vs. 42.6% among those receiving 15 IU/kg; P < 0.05). Patients with initial INR at least 4 benefited the most from treatment. After PTX administration, there was a significant reduction in both transfused blood components units (P < 0.01) and estimated blood loss volume (from 1500 ± 1500 to 200 ± 100 ml; P < 0.01), and only one episode of deep venous thrombosis was observed. Administration of fixed doses of PTX shortened prolonged international normalized ratio and improved life-threatening bleeding in patients with or without VKA therapy. Higher dose attained a more adequate post-infusion INR.