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Objectives To develop a risk-stratified intervention strategy and evaluate its effect on reducing surgical complications. Design A multicentre prospective study with preintervention and postintervention stages: period I (January to June 2015) to develop the intervention strategy and period II (January to June 2016) to evaluate its effectiveness. Setting Four academic/teaching hospitals representing major Chinese administrative and economic regions. Participants All surgical (elective and emergent) inpatients aged ≥14 years with a minimum hospital stay of 24 hours, who underwent a surgical procedure requiring an anesthesiologist. Interventions Targeted complications were grouped into three categories (common, specific, serious) according to their incidence pattern, severity and preventability. The corresponding expert consensus-generated interventions, which focused on both regulating medical practices and managing inherent patient-related risks, were implemented in a patient-tailored way via an electronic checklist system. Primary and secondary outcomes Primary outcomes were (1) in-hospital death/confirmed death within 30 days after discharge and (2) complications during hospitalisation. Secondary outcome was length of stay (LOS). Results We included 51 030 patients in this analysis (eligibility rate 87.7%): 23 413 during period I, 27 617 during period II. Patients' characteristics were comparable during the two periods. After adjustment, the mean number of overall complications per 100 patients decreased from 8.84 to 7.56 (relative change 14.5%; P<0.0001). Specifically, complication rates decreased from 3.96 to 3.65 (7.8%) for common complications (P=0.0677), from 0.50 to 0.36 (28.0%) for specific complications (P=0.0153) and from 3.64 to 2.88 (20.9%) for serious complications (P<0.0001). From period I to period II, there was a decreasing trend for mortality (from 0.64 to 0.53; P=0.1031) and median LOS (by 1 day; P=0.8293), without statistical significance. [ABSTRACT FROM AUTHOR]