Comfort is a crucial factor on board cruise vessels as it largely determines passenger satisfaction, on board expenditure and passenger return. A comfort assessment in the early design phases therefore has added value. These assessments should be practical and require only limited information, but should give reliable and complete answers. Voyage simulations comply with these requirements and offer a practical way to fully account for the variable wind and wave conditions on a given route and their effect on the ship motions that might induce discomfort. A case study is presented for two modern cruise vessel designs of 250 m and 300 m. For these vessels the effect of sailing area on cruise comfort is shown for a Caribbean cruise, a cruise along the Eastside of the USA and a Trans-Atlantic cruise. A Cruise Comfort Index (CCI) has been proposed to easily compare between cruise vessels, investigate the merits of roll stabilisation and optimise the layout of the passenger areas.