Due to the COVID-19 pandemic, the UK government has mandated the use of face masks in various public settings and recommends the use of reusable masks to combat shortages of medically graded single-use masks in healthcare. To assist decision-making on the choice of masks for future pandemics, where shortages may not be a contributing factor, the UCL Plastic Waste Innovation Hub has carried out a multidisciplinary comparison between single-use and reusable masks based on their anatomy, standalone effectiveness, behavioural considerations, environmental impacts and costs. Although current single-use masks have a higher standalone effectiveness against bacteria and viruses, studies show that reusable masks have adequate performance in slowing infection rates of respiratory viruses. Material Flow Analysis, Life Cycle Assessment and cost comparison show that reusable masks have a lower environmental and economic impact than single-use masks. If every person in the UK uses one single-use mask each day for a year, it will create a total waste of 124,000 tonnes, 66,000 tonnes of which would be unrecyclable contaminated plastic waste. Using reusable masks creates >85% less waste, generates 3.5 times lower impact on climate change and incurs 3.7 times lower costs. Further behavioural research is necessary to understand the extent and current practices of mask use, and its effectiveness in reducing infection rates. Wearing single-use masks may be preferred over reusable masks due to perceptions of increased hygiene and convenience. Understanding behaviour towards the regular machine-washing of reusable masks for their effective reuse is key to maximise their public health benefits and minimise environmental and economic costs.