There are conflicting reports concerning signal intensity changes in transient global amnesia (TGA) using diffusion weighted imaging (DWI). We prospectively analysed DWI signal intensity changes in TIA and TGA patients, and compared the clinical characteristics and risk factors of both groups. Using DWI and conventional T1 and T2 weighted turbo spin echo sequences, 28 patients with acute TGA (13 men, mean age 61.5 years) and 74 TIA patients (47 men, mean age 62.4 years) were studied within 48 hours after symptom onset. Every patient underwent an intensive diagnostic investigation. In 10/28 (36%) of the TGA patients and 21/74 (28%) of the TIA patients, DWI signal intensity changes occurred. The time to DWI and the duration of symptoms were comparable in TIA and TGA patients. Overall, TIA patients showed an increased prevalence of vascular risk factors compared with TGA patients. In the TGA group, patients with abnormal DWI showed carotid atherosclerosis significantly more frequently. Based on our data, we suggest that the aetiology of TGA could be explained by an ischaemic event; due to arterial thrombembolic ischaemia in one subgroup, particularly in those patients with increased vascular risk factors, and due to venous ischaemia in another subgroup with valsalva-like activities before symptom onset.