Abstract: Background : : There is insufficient data regarding the differential diagnosis and the prognostic value of significantly elevated serum levels of C-reactive protein (CRP) in hospitalized medical patients. Design and methods: : A retrospective review of medical charts of patients admitted to a tertiary hospital''s Internal Medicine ward during a period of 1 year who had at least one CRP serum level measurement of 200mg/L or more. Results : : Overall, 341 patients with a mean age of 69.8±1.0years were included in the study. Acute infection was the most prevalent diagnosis (n =293; 85.9%) with community-acquired pneumonia being the most common acute infection (n =115; 33.7%). Non-infectious conditions accounted for 9.1% (n =31) of the diagnoses and included mainly malignant metastatic diseases (n =19; 5.6%). Overall, 70 (20.5%) patients died within 30days of admission. Age and active malignancy, with metastasis or without metastasis, were independently associated with 30-day mortality. Conclusion: : Significantly elevated CRP serum levels are associated with bacterial infections, malignant diseases, and very high rates of 30-day mortality in hospitalized medical patients. [Copyright &y& Elsevier]