We investigated the performance of ANA-ELISA for CTDs screening and diagnosis and comparing it to the conventional ANA-IIF. ANA-ELISA is a solid-phase immune assay includes 17 ANA-targeted recombinant antigens; dsDNA, Sm-D, Rib-P, PCNA, U1-RNP (70, A, C), SS-A/Ro (52 and 60), SS-B/La, Centromere B, Scl-70, Fibrillarin, RNA Polymerase III, Jo-1, Mi-2, and PM-Scl. During the period between March till December 2016 all requests for ANA from primary, secondary, and tertiary care centers were processed with both techniques; ANA-IIF and ANA-ELISA. The electronic medical record of these patients was reviewed looking for CTD diagnosis documented by the Senior rheumatologist. SPSS 22 is used for analysis. Between March and December 2016, a total of 12,439 ANA tests were requested. 1457 patients were assessed by the rheumatologist and included in the analysis. At a cut-off ratio ≥ 1.0 for ANA-ELISA and a dilutional titre ≥ 1:80 for ANA-IIF, the sensitivity of ANA-IIF and ANA-ELISA for all CTDs were 63.3% vs 74.8% respectively. For the SLE it was 64.3% vs 76.9%, Sjogren's Syndrome was 50% vs 76.9% respectively. The overall specificity of ANA-ELISA was 89.05%, which was slightly better than ANA-IIF 86.72%. The clinical performance of ANA-ELISA for CTDs screening showed better sensitivity and specificity as compared to the conventional ANA-IIF in our cohort.