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A major challenge for hospitals in low-income and middle-income countries is to improve management of patients diagnosed with sepsis. The objective of the present study was to evaluate the Institute for Healthcare Improvement (IHI) Model as a strategy to implement a managed sepsis protocol aimed at reducing sepsis mortality. We performed a longitudinal, prospective, non-randomised study using PDSA cycles for translating and implementing improvement actions and tools. Baseline case mortality/case fatality data were collected, and compliance rates were evaluated according to the Surviving Sepsis Campaign guidelines (3-hour care-bundle). Sepsis multidisciplinary work teams were designated and were responsible to develop Driver Diagrams and implement process changes in the intensive care unit, wards and emergency department. Satisfaction levels of healthcare professionals were assessed (balance variables). The study was carried out in a public quaternary hospital, in São Paulo city, Brazil (Hospital Municipal da Vila Santa Catarina). The number of patients with sepsis studied was 416 who were followed over a 15-month period. The data analyses were carried out by statistical process control. Case fatality rates were kept below a prespecified target of 25% (15.9%) during the period. Satisfaction level of the participating staff was high (95.2%) and 71% of participants reported no work overload. The IHI model was found to be a feasible and useful strategy for implementing a sepsis management clinical protocol.