The relationship between plaque rupture and adaptive geometric remodelling in the context of unstable atherosclerosis was assessed in proximal brachiocephalic arteries of fat-fed apolipoprotein E (apoE) knockout mice, after constant pressure perfusion-fixation. The rate of vessel expansive remodelling was similar in vessels with plaques and without plaques (+4.0±0.3 and +4.1±0.3 x 103 μm2/week respectively), suggesting that the presence of plaque is not necessary for remodelling to occur. In vessels with plaques, the degree of expansive remodelling was strongly associated with the stability of the plaque. Vessels with stable plaques (i.e. with neither buried fibrous caps nor acute plaque ruptures) showed no expansion (+0.1±1.4 x 103 μm2/week; p=0.953), whereas those with evidence of plaque rupture expanded at a rate of +3.4±0.4 x 103 μm2/week (p<0.0001; p=0.034 versus stable plaques). Vessels with stable plaques suffered significant loss of lumen over time (-2.4±1.1 x 103 μm2/week; p=0.034) but those with unstable plaques maintained lumen area over time (+0.2±0.2 x 103 μm2/week; p=0.362; p=0.014 versus stable plaques). Pravastatin treatment of male apoE knockout mice caused a 5-fold increase in fibrous cap thickness and although it did not influence overall rates of vessel remodelling, it significantly increased both the amount of vessel expansion and the period of time between plaque ruptures, suggesting that it increases the ability of the plaque to resist the rupturing force caused by vessel expansion. These data suggest that vessel expansion in fat-fed apoE knockout mouse brachiocephalic arteries does not require the presence of plaque. When a plaque is present, the outward remodelling force is exerted across its cap: vessels with smaller outward remodelling forces cannot overcome the strength of the cap, and the plaque remains stable. When the remodelling force is greater than the strength of the cap then the plaque ruptures. Thus plaque rupture can be viewed as a consequence of vessel remodelling. Interventions that strengthen the plaque, such as pravastatin therapy, do not alter remodelling parameters but instead allow for more outward remodelling before a rupture is caused.