This study aimed to examine the value of anti peptidylarginine deiminase (anti-PADI-4) antibody and anti-cyclic citrullinated peptide (anti-CCP) antibody among Iraqi patients with RA and to determine whether the activity and severity in RA patients are associated with anti-PADI- 4 and anti-CCP antibodies positivity. In a case control study, we determined the seropositivity of these two serological markers anti- PADI-4 and anti-CCP antibodies in100 RA patients and 100 healthy controls subject. Activity of disease was measured by disease activity score in 28 joints (DAS 28) and severity was assessed using Scott modification of the Larsen method. Antibodies to PADI-4 were detected in (32%) among RA patients and present (1%) in controls (p < 0.001). Anti-CCP was present in (74%) of the RA patients and present in 2% in controls (p < 0.001), sensitivity was highest for anti-CCP antibody (74%) followed by anti-PADI-4 antibody (32%). Specificity was highest for anti-PADI-4 antibody (99%) followed by anti-CCP antibody (98%). A significant correlation with disease activity was observed in both markers, RA patients on remission had negative PADI-4 test (0/12) but patients with high disease activity showed higher percentage (86.4%) of PADI-4 seropositivity in compared to anti-CCP where patients on remission had (8.3%) seropositivity and RA patients with high disease activity had (91%) anti- CCP seropositivity. However, seropostivity to PADI-4 was significant correlated with RA severity (p < 0.001) as evaluated by scott grade (59.3%) in grade 5. Similarly, there were a significant correlation between anti-CCP seropositivity and radiological finding but less than that associated with seropositivity to PADI-4 antibody (p < 0.05). In conclusion, with their excellent specificity, both anti-PADI-4 and anti-CCP antibodies can be useful in establishing the diagnosis of RA, also both markers are good predictors of disease activity and severity.