Natural ventilation is an energy-efficient way to provide fresh air and enhance indoor comfort levels. The wind-driven natural ventilation in courtyards has been investigated by many researchers, particularly the influence of the spatial configuration and environmental parameters on the ventilation and thermal comfort performance. However, previous research has mainly focused on the courtyard region instead of the indoor spaces surrounding it. Additionally, as a microclimate regulator, courtyards are rarely assessed in terms of the impact of vegetation, including its impact on energy consumption and thermal comfort. Evapotranspiration from vegetation can help lower air temperature in the surrounding environment and, therefore, its influence on the ventilation and thermal comfort in buildings with courtyards should be evaluated. The present study investigates the impact of vegetation on the aero-thermal comfort conditions in a courtyard and surrounding buildings in hot climates. Computational fluid dynamics was employed to evaluate the aero-thermal comfort conditions of the courtyard and surrounding buildings with different configurations of vegetation. The modeling was validated using previous works’ experimental data, and good agreement was observed. Thermal comfort indices were used to assess thermal performance. The study also evaluated the cover, height and planting area of vegetation in the courtyard. The results of this study can help develop tools that can assist the addition of vegetation in courtyards to maximize their effects. Future works will focus on looking at the influence of the strategies on different designs and layouts of courtyards.