The scientific literature often reports example of educational buildings with extremely poor ventilation performance. An in-field investigation for the environmental and energy assessment of a kindergarten in Milano, confirmed that operable windows were not operated when the average daily temperature dropped below 14 °C, jeopardizing indoor air quality and kids learning performance. Seven different ventilation strategies were therefore simulated, in order to evaluate the one that better fitted a general project of deep energy retrofit of the building, including building envelope and systems. The best scenario resulted to be the one using hybrid ventilation at nighttime and mechanical ventilation at daytime. Both energy and thermal comfort conditions were evaluated and a tradeoff between them was established. Nighttime ventilation showed to be extremely effective in improving thermal comfort conditions, during the cooling season. It resulted much better than mechanical ventilation in the simulated case study. Simulations show that under moderate weather conditions and if the building is properly operated (ventilation, lighting and solar screening systems) the retrofitted building may perform well also without additional active cooling.