Passenger ships are crowded environments where infections may spread rapidly without effective detection and control measures. Even with rigorous hygiene standards, infectious diseases impact the health of travelers and communities, with potential economic consequences. COVID-19 demonstrated preparedness plans’ inability to rapidly detect emerging diseases and respond effectively. HEALTHY SAILING (HS) provides an innovative approach to address known, expected or emerging infectious diseases, facilitate preparedness for potential future public health emergencies and makes passenger shipping safer, more resilient, competitive and efficient. Current preparedness and response protocols are underpinned by limited scientific evidence. HS applies a multi-method approach to establish an evidence base to understand risk factors, infection spread, and measures’ effectiveness. Results will inform guidance development, and implementation of measures differentiated by passenger ship type. With no holistic approach for surveillance onboard, infections can be undetected leading to outbreaks. HS is developing a prototype software to integrate real-time syndromic, laboratory and environmental health surveillance onboard for early threat detection. To standardize responses, a prototype with artificial intelligence (AI) will provide health threat alerts, support health measure decision making and monitor measure implementation. To enhance hygiene standards, a toolkit for monitoring surface disinfection onboard and an AI water safety plan tool are being developed. A blended learning toolkit with hands-on training for crew and passengers is being produced to increase knowledge and compliance. Mixed methods are identifying social, behavioral and cultural factors to measure compliance, considering gender issues. To assess impact, specific measures will undergo cost-benefit analysis.