The hepatitis C virus (HCV) neutralizing antibody (nAb) response in 37 subjects with HCV monoinfection and 37 HCV-infected subjects with well-controlled human immunodeficiency virus (HIV) infection was evaluated using a focus reduction neutralization assay. HCV nAb levels were retrospectively studied in both groups of patients, who were matched on the basis of sex, age, and HCV genotype. The mean HCV nAb level (+/- standard deviation) among coinfected patients (1.613+/-0.416) was significantly less than that among monoinfected patients (1.912+/-0.578) (P= .013). Lower HCV nAb titers in coinfected patients could help worsen the outcome of HCV infection. These results favor starting HCV therapy as soon as possible in coinfected patients.