ABSTRACT The COVID-19 pandemic caused a surge in hospital waste (HW), posing an urgent public and environmental health challenge. Although a safe HW disposal method, high temperature incineration of fossil-derived materials contributes to air pollution. We analysed the monthly and yearly HW production of four Italian hospitals between 2016 and 2021, including COVID-19-related waste, to quantify the volume of activity related to COVID-19 patients, and estimate the environmental impact of HW through carbon emissions and social cost of carbon (SCC). A Mann-Kendall trend test and an Interrupted Time Series Analysis to detect trends and level changes in HW production after the COVID-19 outbreak were performed. ISMETT had the highest HW production (average annual variation (AAV) 0.89 kg/bed/day) and a positive correlation between HW generated per patient-day and the proportion of COVID-19-related bed-days. IFO (AAV 0.23 kg/bed/day) and IEO (AAV 0.19 kg/bed/day) both showed an overall increasing trend in HW production; CRH behaved similarly, although reporting the lowest HW production. ISMETT and IFO had the highest SCCs; CRH's SCC slightly decreased in the pandemic biennium, IEO's SCC peaked in 2019 and declined in 2020–2021. Optimizing waste management is vital, as disposal emissions pose significant risks to environmental sustainability and human health.