Ultrasonography is considered the most appropriate initial imaging study in the evaluation of acute appendicitis in children but has recently come under criticism with reports of low specificity and high indeterminate study rates, particularly when used in obese patients and patients early in the course of their disease, or when performed by sonographers with limited experience. To (1) assess the impact of patient factors (gender, age, body mass index, and symptom duration) and system factors (call status or year of exam) on pediatric appendiceal US accuracy and indeterminate study rate, (2) assess the impact of indeterminate study results on follow-up CT and negative laparotomy rates and (3) present strategies to reduce the rate of indeterminate US studies and improve accuracy. We retrospectively reviewed all US reports performed for the assessment of acute appendicitis in children <18 years old at Mayo Clinic Rochester from January 2010 to June 2014. A total of 790 US examinations were performed in 452 girls (57%) and 338 boys (43%). The prevalence of appendicitis was 18.5% (146/790). There were 109 true-positive, 440 true-negative, 17 false-positive, 6 false-negative, 218 equivocal and 41 technically inadequate US studies. A definitive interpretation was made in 72% of the studies, with an accuracy, sensitivity and specificity of 0.960, 0.948 and 0.963, respectively. No patient or system factors significantly affected US accuracy. Indeterminate studies (28%) had significantly higher CT utilization (46% vs. 11%) and normal appendectomy rates (6.9% vs. 3.5%). US should be the initial imaging study of choice for pediatric appendicitis. When a definitive interpretation was given, the accuracy was 96%, was independent of patient and system factors and resulted in reduced follow-up CTs and negative laparotomies. Accuracy can be increased by requiring the presence of periappendiceal inflammatory changes prior to interpreting a mildly distended appendix as positive for acute appendicitis. The indeterminate study rate can be reduced by not requiring visualization of the normal appendix for the exclusion of acute appendicitis.