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With only a third of Latinos achieving sustained virologic response (SVR), there is a need for enhanced HCV treatment. Amantadine has been proposed to improve response rates in addition to standard therapy with peginterferon α and ribavirin. Our objective is to evaluate whether triple therapy with amantadine improves SVR rates in this special population. Treatment-naive Latino subjects with HCV genotype 1 infection were randomized to receive peginterferon α-2a plus weight-based ribavirin for 48 weeks (double therapy) or the same regimen plus amantadine 200 mg daily (triple therapy). The primary endpoint was SVR. Predictors of liver fibrosis using APRI and Forns indices were also evaluated. We enrolled 124 patients with chronic hepatitis C genotype 1. Sixty-three received conventional therapy and 61 patients had triple therapy with amantadine. SVR at week 72 was achieved in 25 patients (39.7%) vs. 26 patients (42.6%) in the double and triple regimen, respectively (p = 0.561). After multivariate analysis, advanced fibrosis, obesity, and low pretreatment ALT levels were associated with non-response in both groups (p = 0.0234, p = 0.0012, p = 0.0249, respectively). APRI values delimited an area under the ROC curve (AUROC) of 0.724 and Forns index with AUROC of 0.733. There was no difference between both indices in predicting significant fibrosis (Knodell index: F3–F4). Our study demonstrates that the addition of amantadine to standard treatment of chronic HCV does not improve SVR rates in Latino patients with genotype 1. Further research to improve response rates in this special population is needed.