Transient ischemic attack (TIA) indicates high risk for major stroke and is considered a medical emergency. Diffusion-weighted imaging (DWI) enables detection of acute ischemic lesions. The clinical significance of DWI positive lesions in TIA is obscure and its prevalence, clinical features are not established. Therefore, we performed a clinical, etiological and prognostic analysis through a cross-sectional analysis of 235 TIA patients, grouped according to presence of DWI lesion. Clinical features, underlying risk factors for stroke, outcome and rate of recurrence were analyzed. 3 months follow-up of modified Rankin Scales (mRS) were done with telephone survey. DWI positive lesions were present in 14.0% of patients. Etiological factors significantly associated with DWI lesions in TIA patients were male sex (p = 0.038), stroke history (p = 0.012) and atrial fibrillation (p < 0.001). Presence of at least one medium or high risk of cardioembolism from TOAST classification were not associated with lesions when excluding association to atrial fibrillation (p = 0.108). Clinical features showed no significant difference. Whether the patients had lesion-positive DWI was not related to an increase in mRS score during the hospital stay or at the 3-month follow-up after discharge. Future studies should include multi-center samples with large numbers, considering each unique medical environment. Routine acquisition of follow-up DWI for proper evaluation of the tissue-based definition of TIA should also be considered.