It is occasionally necessary to repeat diffusion weighted imaging (DWI) after giving intravenous contrast medium (CM). However, the effects of CM on DWI and apparent diffusion coefficients (ADC) have not been fully examined. The aim of this prospective study was to investigate whether there are any diagnostically significant differences between echo-planar imaging (EPI)-DWI before and after intravenous CM. EPI-DWI was acquired twice in 203 consecutive patients before and after i.v. CM. Three blinded readers rated the diagnostic image quality. Quantitative ADC calculations were performed before and after CM in all 72 patients with lesions sufficiently large for quantification, and in 72 normal brain regions. Of the 203 patients, 127 had abnormalities on MRI, including ischaemic stroke (52), bleeding (nine), brain tumour with disturbed blood-brain barrier (BBB) (18) and other lesions (48). There were no significant signal differences on isotropic DWI before and after CM, even in lesions with definite disturbance of the BBB. No statistically significant difference between ADC of lesions and contralateral normal brain was observed.