Abstract Background IgE-mediated allergic diseases can be considered a modern epidemic, with exponential growth mainly in industrialized countries. Diagnosis is usually based on detailed medical history, physical examination, skin or challenge test and the determination of allergen-specific serum IgE - a laboratory test that has become a high-value tool in the allergy patient's journey over the last three decades. As the identification of specific immunoglobulin E (sIgE) for a given allergen is important to aid in the allergy diagnosis, several methods for detecting IgE in vitro are available worldwide and, in recent years, there have been several improvements in laboratory methodologies bringing greater advances in terms of clinical and analytical performance. The study aims to evaluate the clinical performance and correlation between two different sIgE assays (IMMULITE® 2000 3gAllergy™ and ImmunoCAP) and their concordance with Skin Prick Test (SPT) and clinical history. Methods This prospective study was conducted with approximately 130 consecutive patients who underwent evaluation of allergic diseases in different centers in Brazil. Clinical data, blood samples, and SPT results were collected. With the blood samples, the allergens D1, D2 and D201 were evaluated using both methods (IMMULITE® 2000 3gAllergy™ and ImmunoCAP) and the data were evaluated in a correlation study and clinical concordance analysis. Results Qualitatively evaluating the sIgE results between the two immunoassays, at the cutoff point considered clinically significant (≥ 0.35 KU/L), a total agreement of 95.2% (D1); 95.1% (D2), 91.7% (D201) and 96.8% (Derp2) was observed. Semi-quantitatively evaluating through reactive interpretation, an agreement of 89.5% (D1); 91.06% (D2); 87.60% (D201) and 93.33% (Derp2) was observed. Spearman's correlation between the analytical methods was 0.85 (D1), 0.93 (D2), 0.68 (D201) and 0.76 (Derp2). When compared with the SPT results, a total agreement of 78.7% and 80.1% was obtained for 3gAllergy and ImmunoCAP, respectively, with slightly higher positive agreement for both methods. Conclusions The two methods have good agreement with each other, with greater differences when evaluated quantitatively. However, when compared to clinical history and skin prick test results, both perform very similarly with a few differences that may be caused by the difference in the assay design.