Background: The quick sequential organ failure assessment (qSOFA) score is suggested to use for screening patients with a high risk of clinical deterioration in the general wards, which could simply be regarded as a general early warning score. However, comparison of unselected admissions to highlight the benefits of introducing qSOFA in hospitals already using Modified Early Warning Score (MEWS) remains unclear. We sought to compare qSOFA with MEWS for predicting clinical deterioration in general ward patients regardless of suspected infection. Methods: The predictive performance of qSOFA and MEWS for in-hospital cardiac arrest (IHCA) or unexpected intensive care unit (ICU) transfer was compared with the areas under the receiver operating characteristic curve (AUC) analysis using the databases of vital signs collected from consecutive hospitalized adult patients over 12 months in five participating hospitals in Korea. Results: Of 173,057 hospitalized patients included for analysis, 668 (0.39%) experienced the composite outcome. The discrimination for the composite outcome for MEWS (AUC, 0.777;95% confidence interval [CI], 0.770–0.781) was higher than that for qSOFA (AUC, 0.684;95% CI, 0.676–0.686; P < 0.001). In addition, MEWS was better for prediction of IHCA (AUC, 0.792; 95% CI, 0.781–0.795 vs. AUC, 0.640; 95% CI, 0.625–0.645; P < 0.001) and unexpected ICU transfer (AUC, 0.767; 95% CI, 0.760–0.773 vs. AUC, 0.716; 95% CI, 0.707–0.718; P < 0.001) than qSOFA. Using the MEWS at a cutoff of ≥ 5 would correctly reclassify 3.7% of patients from qSOFA score ≥ 2. Most patients met MEWS ≥ 5 criteria 13 hours before the composite outcome compared with 11 hours for qSOFA score ≥ 2. Conclusion MEWS is more accurate that qSOFA score for predicting IHCA or unexpected ICU transfer in patients outside the ICU. Our study suggests that qSOFA should not replace MEWS for identifying patients in the general wards at risk of poor outcome.