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Aims: We evaluated a novel disinfectant (VR) and seven comparators (disinfectants A–G) against resistant pathogens common in healthcare settings. Methods and Results: VR at different dilutions, along with commercial disinfectants A–G, was tested against surrogate viruses, and resistant bacterial and fungal pathogens. Surrogate viruses had an initial concentration of ~1 × 108 mL−1, and bacterial and fungal isolates had an initial concentration of ~1 × 106 mL−1 on Siliconee surfaces. After the application of VR or a comparator disinfectant, surfaces were tested for the reduction in microbial loads after 30 s and 5 min wet exposures, and after a 24 h dry residue exposure. Sterile deionized water was used as a control. The VR at a concentration of 4.68% was superior to all comparator disinfectants against most pathogens in wet and dry testing. The VR at 7.8% concentration showed the highest pathogen-reduction rate among all comparator disinfectants when tested against all pathogens. Conclusions: Overall, the novel VR disinfectant was the most effective disinfectant in both wet and dry residue states against the range of tested pathogens. Significance and Impact of the Study: VR is a broadly effective disinfectant combination for use in high-risk settings, particularly those in which intervals between applications of disinfectant can be lengthy or inconsistent.