Rheumatoid arthritis (RA) is one of the most common systemic autoimmune diseases. The presence of antibodies to cyclic citrullinated peptide (CCP) is better at discriminating RA patients and is also associated with significantly more disease activity compared to serum rheumatoid factor. In this study, we assessed two new automated second generation tests to detect the presence of anti-CCP antibodies in 226 serum samples submitted to the Clinical Immunology Laboratory for anti-CCP antibody testing. We compared CCP antibody results on these samples obtained using the ImmunoCAP 250 (Phadia) and the Architect i2000SR (Abbott Laboratories) instruments to our currently used CCP IgG third generation manual ELISA (Inova Diagnostics). One hundred and fifty-four samples were negative while 52 were positive by all three tests. Eighteen samples were negative by the automated tests but weakly/moderately positive by manual ELISA yielding an overall concordance of 79%. When we compared the discordant test results to patient diagnosis, we observed a better correlation with clinical RA diagnosis for the new automated tests compared to the manual ELISA. These two new anti-CCP antibody tests have the benefit of automation and may have better positive predictive value for the diagnosis of RA than our current manual ELISA.