The increase of erythrocyte aggregation by high fibrinogen levels may be an indicator of cardiovascular risk. γ' fibrinogen variant has been considered as a possible player in enhancing aggregation. Here, we assessed, at the single-cell level, the influence of fibrinogen on erythrocyte aggregation in essential arterial hypertension. We also aimed at understanding how γ' fibrinogen is altered in this disease. Using atomic force microscopy (AFM), we show that the work and force necessary for erythrocyte-erythrocyte detachment is higher for patients than for healthy donors, with these parameters further increasing in both groups when higher fibrinogen concentrations are present. This can be associated with changes in blood flow, due to transient bridging of two erythrocytes by fibrinogen, representing an important cardiovascular risk factor. γ' fibrinogen can influence the increased risk in essential arterial hypertension, as we demonstrate that its levels are significantly increased in these patients' blood. Nevertheless, this cannot be the only cause for the changes observed in the AFM data.