BackgroundNational Dutch guidelines have been introduced to improve suboptimal perioperative care. A multifaceted implementation programme (IMPlementatie Richtlijnen Operatieve VEiligheid [IMPROVE]) has been developed to support hospitals in applying these guidelines. This study evaluated the effectiveness of IMPROVE on guideline adherence and the association between guideline adherence and patient safety. MethodsNine hospitals participated in this unblinded, superiority, stepped-wedge, cluster RCT in patients with major noncardiac surgery (mortality risk ≥1%). IMPROVE consisted of educational activities, audit and feedback, reminders, organisational, team-directed, and patient-mediated activities. The primary outcome of the study was guideline adherence measured by nine patient safety indicators on the process (stop moments from the composite STOP bundle, and timely administration of antibiotics) and on the structure of perioperative care. Secondary safety outcomes included in-hospital complications, postoperative wound infections, mortality, length of hospital stay, and unplanned care. ResultsData were analysed for 1934 patients. The IMPROVE programme improved one stop moment: ‘discharge from recovery room’ (+16%; 95% confidence interval [CI], 9–23%). This stop moment was related to decreased mortality (–3%; 95% CI, –4% to –1%), fewer complications (–8%; 95% CI, –13% to –3%), and fewer unscheduled transfers to the ICU (–6%; 95% CI, –9% to –3%). IMPROVE negatively affected one other stop moment – ‘discharge from the hospital’ – possibly because of the limited resources of hospitals to improve all stop moments together. ConclusionsMixed implementation effects of IMPROVE were found. We found some positive associations between guideline adherence and patient safety (i.e. mortality, complications, and unscheduled transfers to the ICU) except for the timely administration of antibiotics. Clinical trial registrationNTR3568 (Dutch Trial Registry).