Objective To analyze the relationship between end-tidal carbon dioxide partial pressure (PETCO2) and arterial CO2 pressure (PaCO2) in invasive ventilated patients. Methods An observational study was conducted in adult patients admitted to Intensive Care Unit (ICU) between June 2016 and March 2017. Samples were immediately analyzed for PaCO2 using a blood gas analyzer. At the same time the arterial to end-tidal CO2 gradient was determined. Relationship in different mechanical ventilation modes, disease categories and PaO2/FiO2 were analyzed in this study. Results A total of 225 arterial blood gases were obtained from the 104 patients. In each of these modes the PETCO2 was generally lower than the PaCO2. There was a positive correlation between PaCO2 and PETCO2 regardless of different mode (r=0.70, Y=11.08+0.77X). A positive correlation was found in SIMV and SPONT modes, but not in A/C mode. The relationship between PaCO2 and PETCO2 in COPD, trauma, cerebrovascular disease and severe pneumonia patients shown a positive correlation (r value was 0.76, 0.64, 0.53, and 0.56, respectively). There was a significant correlation whether PaCO2/FiO2<200 mm Hg (r=0.69, P<0.001) or ≥200 mm Hg (r=0.71, P<0.001). Conclusions The results of this study show that PETCO2 monitoring accurately reflects PaCO2 during mechanical ventilation. A positive correlation is found in different ventilation modes, regardless of disease categories or PaCO2/FiO2.