Recent theoretical calculations showed that reaction with HO<sub>2</sub> could be an important sink for acetone (CH<sub>3</sub>C(O)CH<sub>3</sub>) and source of acetic acid (CH<sub>3</sub>C(O)OH) in cold parts of the atmosphere (e.g. the tropopause region). This work details studies of HO<sub>2</sub> + CH<sub>3</sub>C(O)CH<sub>3</sub> (CH<sub>3</sub>)<sub>2</sub>C(OH)OO (R1) in laboratory-based and theoretical chemistry experiments; the atmospheric significance of Reaction (R1) was assessed in a global 3-D chemical model. Pulsed laser-kinetic experiments were conducted, for the first time, at the low-temperatures representative of the tropopause. Reaction with NO converted HO<sub>2</sub> to OH for detection by laser induced fluorescence. Reduced yields of OH at <i>T</i> < 220 K provided indirect evidence for the sequestration of HO<sub>2</sub> by CH<sub>3</sub>C(O)CH<sub>3</sub> with a forward rate coefficient greater than 2 × 10<sup>−12</sup> cm<sup>3</sup> molecule<sup>−1</sup> s<sup>−1</sup>. No evidence for Reaction (R1) was observed at <i>T</i> > 230 K, probably due to rapid thermal dissociation back to HO<sub>2</sub> + CH<sub>3</sub>C(O)CH<sub>3</sub>. Numerical simulations of the data indicate that these experiments were sensitive to only (R1a) HO<sub>2</sub>-CH<sub>3</sub>C(O)CH<sub>3</sub> complex formation, the first step in (R1). Rearrangement (R1b) of the complex to form peroxy radicals, and hence the atmospheric significance of (R1) has yet to be rigorously verified by experiment. <br><br> Results from new quantum chemical calculations indicate that <i>K</i><sub>1</sub> is characterised by large uncertainties of at least an order of magnitude at <i>T</i> < 220 K. The large predicted values from Hermans et al. lie at the top end of the range of values obtained from calculations at different (higher) levels of theory. Atmospheric modelling studies demonstrated that whilst (R1) chemistry may be a significant loss process for CH<sub>3</sub>C(O)CH<sub>3</sub> near the tropopause, it cannot explain observations of CH<sub>3</sub>C(O)OH throughout the troposphere.