To explore how European hospitals have implemented patient safety strategies (PSS) and evidence-based organization of care pathway (EBOP) recommendations and examine the extent to which implementation varies between countries and hospitals. Mixed-method multilevel cross-sectional design in seven countries as part of the European Union-funded project 'Deepening our Understanding of Quality improvement in Europe' (DUQuE). Seventy-four acute care hospitals with 292 departments managing acute myocardial infarction (AMI), hip fracture, stroke, and obstetric deliveries. Five multi-item composite measures-one generic measure for PSS and four pathway-specific measures for EBOP. Potassium chloride had only been removed from general medication stocks in 9.4-30.5% of different pathways wards and patients were adequately identified with wristband in 43.0-59.7%. Although 86.3% of areas treating AMI patients had immediate access to a specialist physician, only 56.0% had arrangements for patients to receive thrombolysis within 30 min of arrival at the hospital. A substantial amount of the total variance observed was due to between-hospital differences in the same country for PSS (65.9%). In EBOP, between-country differences play also an important role (10.1% in AMI to 57.1% in hip fracture). There were substantial gaps between evidence and practice of PSS and EBOP in a sample of European hospitals and variations due to country differences are more important in EBOP than in PSS, but less important than within-country variations. Agencies supporting the implementation of PSS and EBOP should closely re-examine the effectiveness of their current strategies.