We evaluated the association of urinary excretion of 8-iso-prostaglandin F-2 alpha (8-iso-PGF(2 alpha)) with the vulnerability of culprit lesions in 156 age- and sex-matched diabetic stable coronary artery disease (CAD) patients with or without thin-capped fibroatheroma (TCFA) identified by iMAP intravascular ultrasound. Fasting urinary 8-iso-PGF(2 alpha) level was measured and corrected by creatinine clearance. Compared to non-TCFA group, patients with TCFA had higher urinary 8-iso-PGF(2 alpha) levels [114.6 (71.1, 181.5) vs. 83.0 (63.2, 138.2) pmol/mmolCr, P = 0.012]. Urinary 8-iso-PGF(2 alpha) level was positively correlated with percent necrotic volume of culprit lesion (r = 0.218, P = 0.006). High urinary 8-iso-PGF(2 alpha) level (OR 2.941, P = 0.009) was independently associated with the presence of TCFA and displayed a significant value in predicting TCFA plaques in study patients. The current study indicated that urinary 8-iso-PGF(2 alpha) may be an important surrogate marker for the vulnerability of culprit lesion in diabetic patients with CAD.