In commercial buildings, HVAC systems are becoming a primary driver of energy consumption, which already account for 45% of the total building energy consumption. In the previous literature, researchers have studied several energy conservation measures to reduce HVAC system energy consumption. One of the effective ways is an economizer in air-handling units. Therefore, this study quantified the impact of the outdoor air fraction by economizer control type in cooling system loads based on actual air-handling unit operation data in a hospital. The optimal outdoor air fraction and energy performance for economizer control types were calculated and analyzed. The result showed that economizer controls using optimal outdoor air fraction were up to 45% more efficient in cooling loads than existing HVAC operations in the hospital. The energy savings potential was 6–14% of the differential dry-bulb temperature control, 17–27% of the differential enthalpy control, 8–17% of the differential dry-bulb temperature and high-limit differential enthalpy control, and 16–27% of the differential enthalpy and high-limit differential dry-bulb temperature control compared to the no economizer control. The result of this study will contribute to providing a better understanding of economizer controls in the hospital when the building operates in hot-humid climate regions.