Purpose Coffee is known to contain phytochemicals with antioxidant potential. The aim of this study was to investigate possible antioxidant effects of coffee in healthy human volunteers. Methods A placebo-controlled intervention trial was carried out on 160 healthy human subjects, randomised into three groups, receiving 3 or 5 cups of study coffee or water per day, for 8 weeks. Blood samples were taken before, during, and after the intervention. Serum was used for analysis of blood lipids and standard clinical chemistry analytes. Peripheral blood mononuclear cells were isolated, and DNA damage (strand breaks and oxidised bases) was measured with the comet assay. The lipid oxidation product isoprostane 8-iso-PGF2α was assayed in urine samples by LC–MS/MS. Results There was no significant effect of coffee consumption on the markers of oxidation of DNA and lipids. Creatinine (in serum) increased by a few per cent in all groups, and the liver enzyme γ-glutamyl transaminase was significantly elevated in serum in the 5 cups/day group. Other clinical markers (including glucose and insulin), cholesterol, triacylglycerides, and inflammatory markers were unchanged. There was no effect of coffee on blood pressure. Conclusion In a carefully controlled clinical trial with healthy subjects, up to 5 cups of coffee per day had no detectable effect, either beneficial or harmful, on human health.