Few studies have compared renal infarction (RI) and ureteral stone (US), so there is insufficient evidence for emergency clinicians (ECs) to quickly suspect RI during the first assessment. Therefore, we compared the initial clinical presentation and laboratory findings of these diseases in the emergency department (ED) to determine a factor that may indicate RI. This single-center retrospective case-control study included 42 patients with acute RI and 210 with US who visited the ED from 2014 to 2020. Medical record data from first ED arrival were investigated, and clinical presentations, blood and urine test results obtained in the ED were compared and analyzed using logistic regression analysis. ECs never suspected the initial diagnosis of RI as RI. The most common initial diagnosis was US (40.5%). Among patients with US, 150 patients (71.4%) were suspected of having US (p < 0.001). Abdominal pain (61.9%) was the most common chief complaint in the RI group, and flank pain (73.8%) was the most common in the US group (p < 0.001). 27 factors showed significant differences between the groups. Among those, age ≥ 70 years (odds ratio [OR]: 311.2, 95% confidence interval [CI]: 2.0-47,833.1), history of A-fib (OR: 149872.8, 95% CI: 289.4-7.8E+07), fever ≥37.5 °C (OR: 297.3, 95% CI: 3.3-27,117.8), Cl- ≤ 103 mEq/L (OR: 9.0, 95% CI: 1.0-80.1), albumin ≤4.3 g/dL (OR: 26.6, 95% CI: 2.1-330.3), LDH ≥500 IU/L (OR: 17.9, 95% CI: 1.8-182.5), and CRP ≥0.23 mg/dL (OR: 7.5, 95% CI: 1.1-52.3) showed significantly high ORs, whereas urine RBCs (OR: 0, 95% CI: 0-0.02) showed a low OR (p < 0.05). The regression model showed good calibration (chi-square: 6.531, p = 0.588) and good discrimination (area under the curve = 0.9913). When differentiating acute RI from US in the ED, age ≥ 70 years, history of A-fib, fever ≥37.5 °C, LDH ≥500 IU/L, Cl- ≤ 103 mEq/L, albumin ≤4.3 g/dL, CRP ≥0.23 mg/dL and negative urine RBC result suggest the possibility of RI.