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Objective: Sight-threatening infections can be caused by pathogenic micro-organisms colonising the cornea, leading to microbial keratitis (MK). These micro-organisms can be introduced to the eye via improper contact lens use and care. MK can also result from ineffective contact lens care solutions (CLCs), even if the patient is following best practice guidelines. Therefore, it is critical to understand the differences between the effectiveness of popular CLCs on the global market., Methods and Analysis: Following the International Standards Organisation standards 14 729 and 18259, bacteria ( Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus ), fungi ( Candida albicans, Fusarium strains) and Acanthamoeba strains were inoculated into each CLC with and without contact lenses, and held for the manufacturer's stated disinfection time. Plate counts were conducted to determine the number of surviving micro-organisms., Results: All CLCs examined met the primary log reduction criteria during stand-alone testing for Pseudomonas, Staphylococcus, Candida and Fusarium . renu Multiplus, All Clean Soft, and Kombilösung Super did not meet the primary criteria when challenged with Serratia . Only OPTI-FREE Express exceeded 4 log reduction for both strains of Acanthamoeba tested. We noted a substantial reduction in disinfection efficacy when CLCs were challenged with Fusarium in the presence of lenses and cases versus stand-alone testing. OPTI-FREE Express demonstrated significantly less net log reduction loss than the other four CLCs tested., Conclusion: Of the popular CLCs on the global market, the product which relies on dual biocides polyquaternium-1 and myristamidopropyl dimethylamine demonstrated the highest disinfection efficacy in microbial disinfection challenges in the absence and presence of contact lenses., Competing Interests: Competing interests: All authors are/were employees of Alcon Research., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)