Airborne transmission is one of the main routes of SARS-CoV-2 spread. It is important to determine the circumstances under which the risk of airborne transmission is increased as well as the effective strategy to reduce such risk. This study aimed to develop a modified version of the Wells-Riley model with indoor CO2to estimate the probability of airborne transmission of SARS-CoV-2 Omicron strains with a CO2monitor and to evaluate the validity of this model in actual clinical practices. We used the model in three suspected cases of airborne transmission presented to our hospital to confirm its validity. Next, we estimated the required indoor CO2concentration at which R0does not exceed 1 based on the model. The estimated R0(R0, basic reproduction number) based on the model in each case were 3.19 in three out of five infected patients in an outpatient room, 2.00 in two out of three infected patients in the ward, and 0.191 in none of the five infected patients in another outpatient room. This indicated that our model can estimate R0with an acceptable accuracy. In a typical outpatient setting, the required indoor CO2concentration at which R0does not exceed 1 is below 620 ppm with no mask, 1000 ppm with a surgical mask and 16000 ppm with an N95 mask. In a typical inpatient setting, on the other hand, the required indoor CO2concentration is below 540 ppm with no mask, 770 ppm with a surgical mask, and 8200 ppm with an N95 mask. These findings facilitate the establishment of a strategy for preventing airborne transmission in hospitals. This study is unique in that it suggests the development of an airborne transmission model with indoor CO2and application of the model to actual clinical practice. Organizations and individuals can efficiently recognize the risk of SARS-CoV-2 airborne transmission in a room and thus take preventive measures such as maintaining good ventilation, wearing masks, or shortening the exposure time to an infected individual by simply using a CO2monitor.