Significance Ozonolysis is an important sink of alkenes in Earth’s troposphere, leading to the formation of Criegee intermediates (CIs), whose reactions significantly impact tropospheric composition. The reactivity of the four-carbon unsaturated CIs derived from isoprene, the most abundant alkene, has remained unknown until now. Direct measurements of one such CI, methyl vinyl ketone oxide (MVK-oxide), with water vapor, SO ₂ , and formic acid are reported herein, substantiated by high-level theory, revealing the long lifetime of syn- MVK-oxide with respect to unimolecular decay and reaction with water vapor. Through a combination of direct experiment, high-level theory, and global modelling, syn -MVK-oxide is shown to survive high-humidity tropospheric environments and play a role in sulfuric acid formation and formic acid removal.