Nesfatin is an anti-inflammatory molecule that reduces atherosclerotic cardiovascular risk. By contrast, visfatin has pro-inflammatory properties and is pro-atherogenic. We examined the potential impact of nesfatin and visfatin on atherosclerotic disease in 232 (113 black and 119 white) consecutive rheumatoid arthritis (RA) patients from 2 centers. Independent relationships of nesfatin and visfatin concentrations with metabolic risk factors, endothelial activation, carotid atherosclerosis and altered plaque stability were determined in multivariable regression models. Rheumatoid factor (RF) positivity was associated with both nesfatin (β=0.650, p<0.0001) and visfatin levels (β=0.157, p=0.03). Visfatin concentrations were related to increased diastolic blood pressure (β=4.536, p=0.01) and diabetes prevalence (β=0.092, p=0.04). Nesfatin levels were associated with reduced carotid intima-media thickness (β=−0.017, p=0.008). Nesfatin (β=0.116, p=0.001) and visfatin concentrations (β=0.234, p=0.001) were related to those of matrix metalloproteinase-2 (MMP-2), a plaque stability mediator. Nesfatin and visfatin concentrations were directly correlated (Spearman's rho=0.516). The nesfatin-MMP-2 and visfatin-MMP-2 relations were both stronger in RF negative compared to RF positive patients (interaction p=0.01 and p=0.04, respectively). Nesfatin is associated with reduced atherosclerosis and increased plaque stability mediator levels in RA. Visfatin is related to adverse cardio-metabolic risk in RA. Increased MMP-2 expression in relation to visfatin may represent a compensatory mechanism aimed at reducing cardiovascular risk in RA.