Dengue caused by the Dengue virus (DENV) is a vector-borne viral disease. It is a major public health issue in endemic regions such as India, where secondary infections pose a higher risk of severe illness due to antibody-dependent enhancement. Differentiating primary and secondary infections is crucial for disease management and surveillance. The aim of this study was to estimate the proportion of primary and secondary infections among Dengue cases using Capture IgM and IgG ELISAs and assess the performance of various ratio- and index-based classification methods. Archived serum samples from 784 hospitalized acute-phase Dengue cases in Thiruvallur district, Tamil Nadu, were analyzed, with diagnosis confirmed by non-structural protein (NS1) and/or IgM ELISAs. Capture IgG Enzyme-Linked Immunosorbent Assay (ELISA) classified 46.6% as primary and 53.4% as secondary infections. The IgM/IgG ratio of 2.6 showed the highest concordance (88.6%) with Capture IgG ELISA, while the Receiver Operating Curve (ROC) analysis identified an optimal Optical Density (OD) ratio of 3.08, yielding a sensitivity of 94.3% and specificity of 89.8%. The findings underscore the substantial burden of secondary infections, highlighting the need for continuous surveillance and preventive strategies to mitigate severe outcomes. Capture IgG ELISA remains a robust tool for distinguishing secondary Dengue cases and the IgM/IgG OD ratio of 2.6 serves as a reliable diagnostic alternative with minimal misclassification. These results support the integration of ratio-based methods in Dengue diagnostics to enhance classification accuracy and inform targeted public health interventions.