DescriptionBackground: Celiac disease is a genetic autoimmune disease affecting people of all ages that results in small intestine enteropathy and is caused by the permanent intolerance to gliadin and glutenin, two proteins found in gluten containing grains. Celiac disease is considered to be a clinical chameleon. The disease can also be asymptomatic. Average prevalence of celiac disease in the population is one out of 100 people with data indicating the risk may be as high as 22% for those with first-degree relatives that have the disease. Research suggests 83% of people with celiac disease may be undiagnosed and the average duration for diagnosis is 10 years. Data indicates there is a lack of consensus regarding methodology used to diagnose celiac disease and poor knowledge of associated diseases and symptomatology. A review of the literature determined a celiac disease risk estimation and decision-making expert system including signs, symptomatology, manifestations and associations, with serology and histology based on the Mayo Clinic algorithm, using Exsys Corvid Software, did not currently exist. Method: A new clinical decision support system (CDSS) was developed using Exsys Corvid for expert analysis. The CDSS was divided into symptoms and manifestations with 80 points of navigation, and a serology section, and was validated by 13 experts in the field of celiac disease using a 10 statement, 5-point Likert scale. Results: This scale was analyzed using Cronbach’s alpha reliability coefficient, which was calculated using SPSS. Cronbach’s alpha revealed good internal consistency and reliability with a result of 0.813. One-hundred percent of the experts agreed with the system and that the CDSS is capable of guiding a healthcare professional through the diagnostic process, contains an accurate list of symptoms based on the clinical literature, can foster improved awareness and education about celiac disease, and that there is a need for this system. Over 90% agreed the system is a good tool for training medical students or residents. Conclusion: A celiac disease risk estimation and decision-making expert system was successfully developed and evaluated by medical professionals, with 100% agreeing that this CDSS is medically accurate and can guide healthcare professionals through the diagnostic process.