The relationship between infectious complications and neutropenia was evaluated in recipients of interferon-based therapy for hepatitis C followed at The Ottawa Hospital Viral Hepatitis Clinic from June 2000 to May 2005. One hundred ninety-two patients received 211 courses of therapy (5707 person-weeks of therapy). No patients received granulocyte colony-stimulating factor. Sixty-seven infectious complications occurred in 57 patients (1.17 infections per 100 person-weeks of therapy). The median time to infection was 17 weeks after the start of therapy. Age, sex, weight, race, human immunodeficiency virus status, stage and grade of biopsy, and type of interferon were not correlated with infection rate by Cox regression analysis. The rates of total, fungal, viral, and bacterial infections did not correlate with nadir neutrophil count or magnitude of decrease from baseline. Neutrophil count is not correlated with infection rate in recipients of interferon-based therapy for hepatitis C. Reduction in interferon dose and/or dosing with granulocyte colony-stimulating factor in those with neutropenia is not supported by this analysis.