Aims: Evaluating the use of sequential organ failure assessment (SOFA) ≥ 2 compared to quick SOFA (qSOFA) and to systemic inflammatory response syndrome (SIRS) in assessing 28-days mortality in medical patients with acute infection. Methods: In total, 323 patients with verified infection were stratified in accordance to Sepsis-3. SOFA, qSOFA and SIRS were calculated using registered variables. Adverse outcome was death within 28-days of admission. Results: In total, 190 (59%) patients had a SOFA score ≥ 2 and the overall in-hospital mortality was 21 (6%). Scores of SOFA and qSOFA were both significantly elevated in non-survivors. SOFA showed good accuracy (Area under the receiver operating characteristic (AUROC) = 0.83, 95% CI, 0.76 - 0.90) for 28-days mortality compared with qSOFA (AUROC = 0.67, 95% CI, 0.54 - 0.80) and SIRS (AUROC = 0.62, 95% Cl 0.49 - 0.74). SOFA was ≥ 2 in all patients who died, while qSOFA and SIRS was ≥ 2 in 8 (38%) and 17 (81%) of the patients who died, respectively. Conclusion: SOFA score ≥ 2 was better than SIRS and qSOFA to predict mortality within 28-days of admission among patients with acute infectious disease.