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Disinfection of nosocomial pathogens in hospitals is crucial to combat healthcare-acquired infections, which can be acquired by patients, visitors and healthcare workers. However, the presence of a wide range of pathogens and biofilms, combined with the indiscriminate use of antibiotics, presents infection control teams in healthcare facilities with ongoing challenges in the selection of biocides and application methods. This necessitates the development of biocides and innovative disinfection methods that overcome the shortcomings of conventional methods. This comprehensive review finds the use of hydrogen peroxide vapour to be a superior alternative to conventional methods. Motivated by observations in previous studies, herein, we provide a comprehensive overview on the utilisation of hydrogen peroxide vapour as a superior high-level disinfection alternative in hospital settings. This review finds hydrogen peroxide vapour to be very close to an ideal disinfectant due to its proven efficacy against a wide range of microorganisms, safety to use, lack of toxicity concerns and good material compatibility. The superiority of hydrogen peroxide vapour was recently demonstrated in the case of decontamination of N95/FFP2 masks for reuse to address the critical shortage caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during the COVID-19 pandemic. Despite the significant number of studies demonstrating antimicrobial activity, there remains a need to critically understand the mechanism of action by performing studies that simultaneously measure damage to all bacterial cell components and assess the correlation of this damage with a reduction in viable cell count. This can lead to improvement in antimicrobial efficacy and foster the development of superior approaches.