In contrast to the intact wine, cardiovascular effects of the thermally treated wine have not been studied, despite widespread habits of cooking with wine and consumption of mulled wine. Vasodilatory effects of the red wine heated at 75 and 125°C were examined in the isolated rat and guinea pig aorta and compared with the intact and wine dealcoholized without thermal stress. Samples were analyzed for their phenolic content, antioxidant capacity, resveratrol and ethanol contents. Heating-induced degradation of individual phenolic fraction was observed only in the samples treated at 125°C, although total phenolic concentration and related antioxidant activity increased in the thermally treated samples due to the reduction in their volume. All wine samples regardless of treatment caused similar maximal relaxation in both species, but the response was stronger in aortas from guinea pigs. At the lowest concentrations up to 1‰, dealcoholized wine produced vasodilation greater than that produced by intact wine and wines treated at 75 and 125°C, which showed similar vasodilating activity at all concentrations. Our results indicate that wine thermally treated under heating conditions applicable to the preparation of a mulled wine and cooking with wine largely retains vasodilatory activity in vitro despite significant heat-induced changes in its composition.