In the beginning of 2020, the coronavirus (COVID-19) pandemic started to spread globally, causing panic to the lives of people around the world; many countries executed lockdown of cities or even total lockdown of the entire countries. The coronavirus disease (COVID-19) is transmitted via air droplets. In medical environments that use traditional hermetic ventilation systems, medical personnel who come in contact with patients are more susceptible to infection compared to regular staff; therefore, the air flow and air quality of hermetic negative pressure isolation wards are highly critical. For this purpose, the study proposes a full-outer-air-intake natural air-conditioning system for negative pressure isolation wards. This innovative system draws in large amounts of fresh external air to greatly improve the air exchange rate in wards; negative pressure environments can be implemented depending on requirements to solve the issue of nosocomial infections in traditional negative pressure isolation wards that draw air from within the hospital. This greatly reduces the probability of nosocomial infection and infection via air droplets; furthermore, the system’s intake and exhaust paths are completely isolated, solving the issue of air cross-contamination. Based on the results from the experiment site, this innovative system was designed and implemented based on the guidelines of hospital facilities and achieved air exchange per hour in excess of 12 times/hour, reaching a maximum of 54.5 times/hour. Indoor CO2 concentration was 576 ppm, negative pressure was −14 Pa, indoor temperature was 23.3°C, indoor humidity was 54.1%, and sensible heat exchange efficiency (ηs) was 105.88% which effectively reduced ventilation load. Therefore, this innovative full-outer-air-intake natural air-conditioning system can provide medical staff and patients with a safe and healthy environment that prevents cross-infection.