The infection with hepatitis C virus (HCV) known also as a blood-borne infection can be life-threatening by delayed consequences of persistent infection. This study aimed to estimate the hepatitis C infection prevalence, its epidemiological mode of manifestation and its recent evolution among blood donors from North West region of Romania. We made a chronological study using the HCV seropositive confirmed results to serological blood donors screening, provided by two Blood Transfusion Centres, chosen for their quality of provided data: Cluj and Satu Mare. The statistics were descriptive and the time series modelling used the polynomial regression. In both counties, about three fourth of donors were male and in Satu Mare, female donors (29.2%; p < 0.001) have been significantly more represented than in Cluj (24.6%). Hepatitis C virus seroprevalence was significantly (p < 0.01) higher in Satu Mare (279.8/10(5) donors, CI: 241.7-317.9/10(5) donors) than in Cluj (212.6/10(5) donors, CI: 187.4-237.8/10(5) donors). The mode of manifestation was endemic in different patterns, one with wave and a stable one with a particular high value of 1.091.1/10(5) female donors (CI: 674-1508.2/10(5) donors) seroprevalence, in 2008, in Satu Mare. The variation of the prevalence value was higher for women and particularly (coefficient of variation: 91.9%) for those from Satu Mare. The hepatitis C virus seroprevalence among blood donors reflected a stable, endemic manifestation with particular variation and high transmission in female populational subgroups.