Instantaneous or tankless gas-fired water heaters are widely used in residential buildings to heat water for domestic use. For the combustion can process properly, a minimum amount of air is required, which can be obtained directly from outdoors or from inside the room. This latter case corresponds to the operation mode of the atmospheric-vent water heater, which is one of the most frequently encountered appliances to heat domestic water. As the room where the water heater operates is generally a living area, the installation design should account for the health and comfort requirements. Increasing the room airflow rates reduces the risk of harmful products from incomplete combustion but, as counterpart, important impacts on the thermal and energy performance of the room can occur. In this paper the natural ventilation conditions of a room with an atmospheric-vent water heater are investigated. Moreover, the effects on energy demand for thermal comfort are assessed. The study was conducted through the EnergyPlus simulation program, whose applicability to the problem was first tested. The results obtained are consistent with the expectations, allowing for a better insight into the level of compliance of the combustion air requirements and respective impacts on energy performance.