Abdominal ultrasound is used for diagnosing appendicitis in patients with right lower quadrant abdominal pain. Between 45 and 82% of radiology performed ultrasounds are indeterminate for appendicitis and computed tomography is required for diagnostic confirmation. Our study aims to determine predictors to rule out appendicitis when ultrasound is indeterminate. We performed a health records review of adult emergency department (ED) patients presenting with symptoms suspicious for appendicitis and indeterminate ultrasound to two academic EDs between June 2019 and July 2020. The outcome was appendicitis diagnosis within 30days of the index ED visit. We used multivariable logistic regression, identifying a cut-off threshold for continuous variables with cubic spline, and chose the parsimonious model to develop a binary decision rule. We report Odds ratios (OR) and diagnostic performance with 95% confidence intervals (CI). Overall, 463 patients (mean age 30.3years (SD 10.5years), 74.9% female) were included. Appendicitis was diagnosed in 45 patients (9.7% [95% CI 7.2-12.8%]). After ultrasound, computed tomography was performed in 227 patients (49.0%) and 39 patients (17.2%) were diagnosed with appendicitis. Among the 236 patients who did not have a subsequent computed tomography, 6 (2.6%) patients had appendicitis. Neutrophil count > 5.5 × 109/L (OR 1.21 [95% CI 1.12-1.30]) and secondary signs of inflammation on ultrasound (OR 2.16 [1.07-4.37]) were associated with a higher likelihood of appendicitis (C-statistic 0.77 [95% CI 0.70-0.84]). The absence of both predictors had a sensitivity of 88.9% (95% CI 76.0-96.3%), specificity of 45.7% (95% CI 40.8-50.6%) and a negative predictive value of 0.97 (95% CI 0.94-0.99) to rule out appendicitis. For patients suspected of appendicitis and indeterminate ultrasound, the absence of an elevated neutrophil count and secondary signs of inflammation are associated with a low probability of appendicitis.