Quantification of hepatitis C virus (HCV) RNA is important in the assessment of HCV-associated liver disease in patients coinfected with HCV and human immunodeficiency virus (HIV). To investigate whether the standard integrity of competing test methodologies might be compromised by higher HCV titers in coinfected patients, 2 technologies (a polymerase chain reaction-based assay [COBAS Amplicor 2.0 assay; Roche Diagnostics] and a branched-chain DNA assay [Versant 3.0; Bayer]) were evaluated by testing paired serum samples from 68 coinfected patients and 137 HCV-monoinfected patients. Although the correlation was highly significant (r=0.81; P<.001), HCV RNA titers expressed in international units per milliliter could not be standardized; statistically significant differences were observed in all quartiles. Significant variability (P<.0007) was observed in the classification of patients as having a high versus a low virus titer (cutoff, 800,000 IU/mL), which suggests that standardization in international units has low efficacy among coinfected patients. Clinicians should note that test variability precludes direct comparability of HCV RNA titers, particularly in coinfected patients with high titers.