This paper presents an application of the Simulink stvmgain S-function for the thermal modelling of a building zone based on the resistance–capacitance scheme of EN ISO 13790. That model in the form of the state-space matrix with time-varying elements was used in simulations of a building with hourly and, suggested in that standard, daily averaged ventilation airflow in five European cities. The following two ventilation schedules were used: occupancy-based; and wind-dependent. Comparative simulations were conducted in EnergyPlus. In general, the results obtained for the annual heating and cooling demand were better for hourly than daily averaged ventilation with an error below 10%. However, in several cases of cooling, the error was above 30%. When considering hourly indoor air temperatures, the proposed method provided very good results with MAE of up to 0.52 °C and 0.46 °C, RMSE < 0.69 °C and 0.62 °C, and CV(RMSE) < 3.09% and 2.75% for the daily averaged and hourly ventilation flow, respectively. For wind-driven ventilation, the temperatures were as follows: MAE < 0.49 °C and 0.48 °C; RMSE < 0.69 °C and 0.68 °C; and CV(RMSE) < 3.01% and 2.97%.