Objective To evaluate the clinical performance of checklist for early recognition and treatment of acute illness (CERTAIN) on patients in the intensive care unit (ICU). Methods A prospective observational study was performed. 100 patients (age > 18 years old, the length of ICU stay > 72 hours) admitted to ICU of the Second People's Hospital of Lu'an from January to July in 2018 were enrolled. By convenience sampling methods, 50 patients admitted to the hospital from January to April in 2018 were selected as the control group. Standard ward inspection was given to the control group by three senior-level and intermediate-level doctors blinded from the research plan; at the end of March 2018, these three doctors were trained with the CERTAIN checklist and certified by the Mayo Clinic distance learning training. Fifty patients enrolled from March to July 2018 received medical rounds using CERTAIN (observation group). The CERTAIN checklist contained 20 items that cover the range of daily critical ward rounds, which need clinicians to quantify each item. The data included the length of ICU stay, central venous catheter (CVC) indwelling time, catheter indwelling time, duration of mechanical ventilation, drug use rate, ICU mortality, and incidence of adverse events were collected and compared between the two groups. The independent factors affecting ICU death were analyzed by log-rank univariate analysis and Cox regression multivariate analysis. Results Compared with control group, the length of ICU stay (days: 8.68±4.84 vs. 13.64±9.37), catheter indwelling time (days: 8.16±5.29 vs. 13.32±9.31), duration of mechanical ventilation (days: 3.46±4.14 vs. 6.62±9.57) in observation group were significantly decreased, insulin use rate (34.0% vs. 56.0%) and ICU mortality (2.0% vs. 14.0%) were significantly decreased, with statistically significant differences (all P < 0.05). Besides, the use of CERTAIN can significantly improve the efficiency of the ward inspection. The ward inspection time was shortened from (8.00±0.45) minutes to (5.00±0.33) minutes by using the CERTAIN checklist (t = 9.312, P < 0.01). Survival analysis showed that CERTAIN application could reduce ICU mortality (χ2= 3.898, P = 0.048), but the use of CERTAIN was not an independent factor for reducing ICU mortality [odds ratios (OR) = 1.001, P = 0.922]. Conclusions CERTAIN application has a significant effect on critical patients. It is suggested to spread in ICU of China.