Paroxonase 1 (PON 1) enzymatic activity and Q192R PON polymorphism has been implicated with greater cardiovascular risk in general population. Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized with increased inflammatory markers leading to increased cardiovascular morbidity. The aim of the work was to study association between PON1 enzymatic activity & gene polymorphism with carotid plaques in RA patients. This case–control study was carried out at Zagazig University Hospitals on 99 subjects divided randomly into two groups; 48 RA patients and 51 controls. RA patients fulfilled the revised 2010 EULAR/ACR classification criteria of RA. All patients were subjected to history taking, clinical evaluation, laboratory investigations & plain X-rays. Carotid intima-media thickness (CIMT) and PON1 enzyme assay & genotyping were done for both groups. PON1 enzyme levels were significantly higher in patients than controls. Also, there was a significant negative correlation of PON1 enzyme activity with increased CIMT & plaques. The cut-off value of PON1 enzyme level that had the highest CVD prediction was 4.2 U/ml. Although PON1 genotyping was insignificantly different between patients and controls, patients with QQ genotype had the lowest PON1 activity then patients with QR genotype then RR genotype. In RA patients, decreased serum PON1 enzymatic activity and QQ genotyping of Q192R PON polymorphism was associated with increased CIMT & plaques. Serum PON1 could be a good marker for atherosclerosis prediction in RA patients at cutoff 4.2 U/ml