Elderly patients with chronic hepatitis C cannot tolerate standard combination therapy of peginterferon and ribavirin, which remains the backbone of therapy in many countries, including Japan. The efficacy and safety of low-dose peginterferon α-2b in combination with low and escalating doses of ribavirin in older patients with high viral load genotype 1 were investigated in this randomized controlled trial. Thirty-two patients (age ≥60 years) were randomized into standard (group 1) or low (group 2) doses of peginterferon α-2b in combination with low and escalating doses of ribavirin. Patients were evaluated for safety and efficacy of treatment. There was a higher virological response rate in group 1 than in group 2. However, the response in men was higher than in women in the early treatment phase and 24 weeks after treatment (P = 0.008). There was no significant difference between the two groups in the virological response rate in men and women. Completion of therapy was higher in group 2 than in group 1 (31% vs. 13%, P = 0.200). Dose modification of ribavirin was less frequent in group 2 than in group 1 (69% vs. 88%, P = 0.200). These data suggest that combination therapy with low-dose peginterferon plus low and escalating doses of ribavirin may be safer in older patients than that with standard dose peginterferon, without impairing the treatment response. J. Med. Virol. 87:2082–2089, 2015. © 2015 Wiley Periodicals, Inc.