ACORN-HAI is a large-scale multi-centre surveillance which focuses on the treatment and clinical outcomes of healthcare-associated bloodstream infection and ventilator-associated pneumonia. These severe infections are frequently caused by multidrug-resistant bacteria which have no effective treatment options. Prospectively collected case-based data of these infections are lacking and urgently needed to guide interventional trials. Our aims are firstly to establish a surveillance platform in hospitals with high burdens of drug resistance, in order to investigate target organisms and make up-to-date assessments on treatment options. Secondly through implementing the study across various regions and income settings, we aim to share expertise, optimise local engagement, and establish research teams and laboratory capacity. The enrollment criteria are based on the US Centers for Disease Control and Prevention criteria for healthcare-associated infection surveillance. Functional and mortality outcomes will be assessed on day 28. Bacterial isolates will be collected for genomic analysis to study geographical and temporal trends in resistance clones and genes. The target sample size is 500 participants per site over 30 study sites. ACORN-HAI study is a critical step towards assessing the burden of severe drug-resistant infections, and inform interventional trials to optimise treatment