Celiac disease (CD) affects approximately 1% of the population and may present with varied symptomatic as well as asymptomatic clinical manifestations. Simple methods of detecting CD such as serum antibody tests have helped in the early identification of the disease thus preventing serious complications of the disorder. Our objective is to develop specific and sensitive immunoassays that are reliable in the detection of CD. To this end, immunoassays were developed for the detection of IgG and IgA antibodies to gliadin using synthetic peptides. Over 200 serum samples were included in the study from individuals with CD submitted for endomysial (EMA) and tissue transglutaminase (tTG) antibody tests as well as from disease controls and healthy normals. To examine the reliability of the Celiac G+ antibody test in comparison with EMA, a test with higher sensitivity and specificity, samples with low and high EMA titers were included in the study. Comparative evaluations of the Celiac G+ antibody assay were made with EMA and another commercially available gliadin peptide assay along with tTG antibody assays. The data show that as the EMA levels increased the sensitivity of detection of antibodies to synthetic peptides on both systems increased, reaching 100% at EMA titers greater than 160. The diagnostic performance of the newly developed Celiac G+ synthetic gliadin peptide assay is significantly superior in comparison with another available gliadin peptide immunoassay. Overall, the diagnostic performance of the Celiac G+ assay for IgA and IgG reached a sensitivity of 80% and 90% respectively in comparison with EMA. Similar comparison of the EMA positivity to the other available synthetic peptide immunoassay yielded sensitivities of 59% (IgA) and 75% (IgG). The specificity of the Celiac G+ antibody assay for IgA and IgG was 90-95% as compared to the other similar assay with specificity of 88-90%. In conclusion, the performance of the recently developed Celiac G+ ELISA is superior in both its sensitivity and specificity in comparison with other available synthetic gliadin peptide immunoassays. Furthermore, the IgG Celiac G+ antibody test and IgA tTG antibody test used in combination is an excellent screening algorithm for suspected cases of celiac disease.