Abstract Background: We performed the Roche Amplicor Monitor hepatitis C virus (HCV) v2.0 microwell plate (MWP) assay for 2 years prior to bringing a COBAS instrument into the lab. Before reporting any results from the automated COBAS Amplicor Monitor HCV v2.0, we compared quantitative data with results on the same specimens from the manual Amplicor Monitor HCV. Objective: To determine if the COBAS Amplicor Monitor assay yielded quantitative results that were comparable with those given by the manual Amplicor Monitor HCV. Study design: We tested 145 specimens with both assays. Specimens were chosen on the basis of having fallen within the linear range of the first assay. Results: The log 10 mean (±standard deviation) for all 145 specimens was 5.976 (±0.597) for the COBAS and 6.142 (±0.597) for the MWP assay. When plotted as 145 pairs of numbers (log MWP result vs. log COBAS result), the linear regression line was displaced slightly downward from the line of equivalence by 0.1 log at the lower end and by 0.2 log at the upper end indicating the COBAS result was somewhat lower than the MWP result across the full range of the assay. The mean of the difference of the manual method and the COBAS for all 145 specimens was 0.166 log 10. A subset of 45 specimens for which we had HCV genotype data was analyzed separately. This set of specimens (of which 33 were genotype 1) also showed excellent concordance between the automated and manual methods. The two trendlines, one for genotype 1 and the other for genotypes 2, 3 and 4, were superimposable and thus the quantitative results were apparently not influenced by the genotypes, although the numbers were small (six HCV genotype 2, five HCV genotype 3 and one HCV genotype 4). Conclusions: We conclude that the automated Roche COBAS Amplicor Monitor v2.0 yields results that are comparable with the manual Amplicor Monitor assay for HCV genotype 1 and possibly also for genotypes 2, 3 and 4.