The potential of mixed-mode office buildings with varying design and control parameters is examined by using an uncertainty analysis in the three climate zones of India. The analysis is in terms of cooling energy consumption, thermal comfort conditions, and natural ventilation hours. Furthermore, influential parameters are identified using sensitivity analysis. In this study, opening the windows enables natural ventilation. Night-time ventilation through the windows is not enabled because these are mostly closed at night. A maximum natural ventilation of 10% of the total building occupancy hours are observed in warm and humid, and hot and dry climates; however, they are slightly higher in the composite climate. A further increase in the number of natural ventilation hours leads to an increase in the occupancy hours outside the Indian Model for Adaptive Comfort model for mixed-mode buildings with at least 90% of occupants are satisfied. There are no occupancy hours outside of 80% of occupants are satisfied. The choice of thermal comfort band is crucial for determining the potential of mixed-mode buildings. The cooling setpoint temperature, building size, window solar heat gain coefficient, and surface properties of exterior surfaces are identified as the more influential parameters than the thermophysical properties of building envelope constructions. Although the building envelope which is in compliance with the Energy Efficient Building Code of India increases energy efficiency during airconditioning periods, whether it reduces natural ventilation hours, because of overheating during such period remains to be determined.