The atmospheric chemistry of 2,2,5,5-tetramethyloxolane (TMO), a promising “green” solvent replacement for toluene, was investigated in laboratory-based experiments and computational calculations. Results from both absolute and relative rate studies demonstrated that the reaction OH + TMO (Reaction R1) proceeds with a rate coefficient k1(296 K) = (3.1 ± 0.4) ×10−12 cm3 molecule−1 s −1 , a factor of 3 smaller than predicted by recent structure–activity relationships. Quantum chemical calculations (CBS-QB3 and G4) demonstrated that the reaction pathway via the lowest-energy transition state was characterised by a hydrogen-bonded prereaction complex, leading to thermodynamically less favoured products. Steric hindrance from the four methyl substituents in TMO prevents formation of such H-bonded complexes on the pathways to thermodynamically favoured products, a likely explanation for the anomalous slow rate of Reaction (R1). Further evidence for a complex mechanism was provided by k1(294–502 K), characterised by a local minimum at around T = 340 K. An estimated atmospheric lifetime of τ1 ≈ 3 d was calculated for TMO, approximately 50 % longer than toluene, indicating that any air pollution impacts from TMO emission would be less localised. An estimated photochemical ozone creation potential (POCPE) of 18 was calculated for TMO in north-western Europe conditions, less than half the equivalent value for toluene. Relative rate experiments were used to determine a rate coefficient of k2(296 K) = (1.2±0.1) ×10−10 cm3 molecule−1 s −1 for Cl + TMO (Reaction R2); together with Reaction (R1), which is slow, this may indicate an additional contribution to TMO removal in regions impacted by high levels of atmospheric chlorine. All results from this work indicate that TMO is a less problematic volatile organic compound (VOC) than toluene.