Background: The in-hospital mortality of patients admitted from the emergency department (ED) is high, but no appropriate initial alarm score is available. Methods: This prospective observational study enrolled ED-admitted patients in hospitalist-care wards and analyzed the predictors for seven-day in-hospital mortality from May 2010 to October 2016. Two-thirds were randomly assigned to a derivation cohort for development of the model and cross-validation was performed in the validation cohort. Results: During the study period, 8,649 patients were enrolled for analysis. The mean age was 71.05 years, and 51.91% were male. The most common admission diagnoses were pneumonia (36%) and urinary tract infection (20.05%). In the derivation cohort, multivariable Cox proportional hazard regression revealed that a low Barthel index score, triage level 1 at the ED, presence of cancer, metastasis, and admission diagnoses of pneumonia and sepsis were independently associated with seven-day in-hospital mortality. Based on the probability developed from the multivariable model, the area under the receiver operating characteristic curve in the derivation group was 0.81 [0.79–0.85]. The result in the validation cohort was comparable. The prediction score modified by the six independent factors had high sensitivity of 88.03% and a negative predictive value of 99.51% for a cutoff value of 4, whereas the specificity and positive predictive value were 89.61% and 10.55%, respectively, when the cutoff value was a score of 6. Conclusion: The seven-day in-hospital mortality in a hospitalist-care ward is 2.8%. The initial alarm score could help clinicians to prioritize or exclude patients who need urgent and intensive care.