Summary. International controlled trials have demonstrated increasing sustained virological response (SVR) rates to interferon-based therapies in hepatitis-C-treated patients. Response rates of 6–20% in the era of interferon monotherapy are compared with 42–82% with pegylated interferon plus ribavirin. The virological durability of the SVR is unknown and the optimal follow-up for these patients is unclear. The aim of our study was to determine SVR rates and the durability of the response to interferon-based therapies in the clinical setting. From our database of 1540 hepatitis C patients, 344 treatment courses of at least 12 weeks duration were identified, including interferon monotherapy (175 patients), interferon plus ribavirin (96 patients) and peginterferon plus ribavirin (73 patients). Interferon monotherapy was associated with an SVR rate of 5% in 103 genotype 1 patients and 25% in 72 genotype 2/3 patients. Response rates were higher (P < 0.001) with interferon plus ribavirin—41% in 34 genotype 1 patients and 73% in 62 genotype 2/3 patients—and with peginterferon plus ribavirin—47% in 47 genotype 1 patients and 79% in 26 genotype 2/3 patients. Of 147 patients with an SVR, 146 (>99%) remained hepatitis C virus PCR negative during a mean 2.3 years (range 0.3–10.3) of follow-up. In conclusion, with advances in therapies, we are achieving higher response rates in hepatitis C patients treated in the clinical setting. We can now expect an SVR in over half of the treated patients. Importantly, the response is durable and medium and long-term follow-up of these patients are of low yield and largely unnecessary.