<h3>Objective</h3> According to European Medicines Agency (EMA) the on-label indication for aprotinin is for patients undergoing isolated coronary artery bypass graft surgery (iCABG), who are at high risk of major blood loss. The objective of the study was to describe current on- and off-label use of aprotinin and associated safety endpoints, including mortality, in adult patients undergoing high risk cardiac surgery in Nordic countries. <h3>Design and Method</h3> Data were analysed from cardiac surgery centres in Finland, Norway and Sweden that were participating in the European Nordic aprotinin patient registry (NAPaR), which is a non-interventional, post-authorization safety study (PASS) executed at EMA's request. Ethical approval was given by responsible authorities at each Hospital and all patients agreed to partake. The treating doctors determined if patients were to be given aprotinin. <h3>Results</h3> Altogether 489 patients were given aprotinin between 2016 to 2020 and of those 72.8% were male and 9.8% >75 years old. 59 patients (12.1%, on-label) underwent iCABG and 430 (87.9%, off-label) another procedure, including a surgery for aortic dissection (n=81, 18.8%) and endocarditis (n=175, 35.8%). 437 patients (89.4%) were given the full Hammersmith regimen and 37.2% had experienced at least one earlier heart procedure. 14.9% of all patients were on dual antiplatelet treatment, which affected 72.9% of iCABG and 7.4% of non-iCABG patients. Preoperative renal impairment (creatinine clearance < 85 mL/min) affected 50.7% of patients and 51.7% of the procedures were urgent, 17.0% emergent and 4.9% salvage. Mean/median bypass time was 159/148 min (range 25-637 min). 0.6% of patients had anaphylactic reactions associated with aprotinin. Within 24 and 48 hours postoperatively, 2.5% (CI95%:1.1%-3.8%) and 4.9% (3.0%-6.8%) of patients were reoperated for bleeding, respectively. Rate of postoperative thromboembolic events, day 1 rise in creatinine >44 μmol/L and new dialysis for any reason was 4.7% (CI95%: 2.8%-6.6%), 17.0% (CI95%: 13.6%-20.3%) and 14.3% (11.2%-17.4%), respectively. In-hospital mortality and 30-day mortality was 4.9% (CI95%: 2.8%-6.9%) and 6.3% (CI95%: 3.7%-7.8%) in all patients versus mean EuroSCORE II (estimates 30-day mortality) 11.4% (CI95%: 8.4%-14.0%, p<0.01). 30-day mortality in patients undergoing surgery for aortic dissection and endocarditis was 6.2% (CI95%: 0.9%-11.4%) and 6.3% (CI95%: 2.7%-9.9%) versus mean EuroSCORE II 13.4% (CI95%: 6.1%-21.0%, p=0.11) and 14.5% (CI95%: 12.1%-16.8%, p=0.01), respectively. <h3>Conclusions</h3> In patients given aprotinin at high risk of death and bleeding undergoing cardiac surgery, mainly complex procedures, 30-day mortality was significantly lower, with approximately halved mortality rates compared with estimations by EuroSCORE II. NAPaR data from Nordic countries suggest a favourable safety profile of aprotinin in adult cardiac surgery.