Chronic hepatitis C is frequent and aggressive among HIV-positive patients; evaluation for anti-hepatitis C virus (HCV)-specific therapy is mandatory, but it has many limitations, due to efficacy, tolerability but also applicability. The objective of our retrospective analysis was to evaluate the eligibility and feasibility of anti-HCV therapy in HIV/HCV-coinfected patients followed at the II Department of Infectious Diseases, L. Sacco Hospital, Milan, Italy, from 2000 to March 2010. In our database, 545 HIV/HCV-coinfected patients were present, representing 40% of our whole HIV population, and 421 included in the analysis. One hundred twenty-four patients were excluded because of loss to follow-up (81) or deceased (43). Forty-eight patients spontaneously cleared HCV during follow-up (11%). Ninety-nine patients received anti-HCV therapy (26%), while the majority was excluded for several reasons (mainly concomitant diseases and low CD4(+) cell count). Globally, we found that in at least one third of untreated patients modifiable barriers to treatment were present. The access to therapy was significantly associated with the absence of history of intravenous drug use (p=0.01), a higher CD4(+) cells count at nadir (p=0.01), the presence of more than 6 HAART regimens (p=0.04), higher alanine aminotransferase (ALT) levels (p<0.0001), HCV genotype 2 or 3 (p=0.005). In a multivariate analysis, the same factors remained significantly associated with anti-HCV therapy. In conclusion, the feasibility of anti-HCV therapy in HIV/HCV-coinfected patients, in our highly specialized center, is approximately 26%. Relative contraindications, such as substance abuses, mild and controlled concomitant conditions, and low compliance are common and modifiable in order to reconsider patients as suitable for therapy.