Platelet volume is a measure of platelet function. An increased platelet volume is found in acute vascular syndromes and may have a causative role and predict outcome. Patients with autosomal dominant polycystic kidney disease (APKD) are at increased risk of developing, and dying from, premature vascular disease. We hypothesized that platelet volume might be altered in patients with APKD. Platelet volume was measured in 16 normotensive APKD patients with normal renal function and 16 normal volunteers pair-matched for age, gender, race and body mass index.Mean platelet volume was increased by 0.4 fl (95% confidence limits 0.1 to 0.9, 2P=0.017) in patients with APKD as compared with normal subjects: median 8.4 fl (0.7) versus 8.0 fl (0.3) respectively. In contrast, platelet count was lower by 63×109/1 (−5 to -108, 2P = 0.031): 225 (40)×109/1 versus 280 (35)×109/1 while the platelet mass was not different, -0.36 ml/l (−0.81 to 0.02, 2P=0.070): 1.82 (0.30) ml/l versus 2.28 (0.38) ml/l. Platelet volume and count were inversely correlated across the two groups, rs= -0.342 (2P=0.055). Serum levels of erythropoietin, a hormone that contributes to the regulation of thrombopoeisis, were not different between the APKD patients and normal controls, 35 U/1 (−71 to 120, 2P=0.42): 107 U/I (53) versus 84 U/I (57). Although erythropoietin did not correlate with platelet volume, R., = -0.185 (2P =0.36), it was positively associated with platelet count, R., = 0.465 (2P=0.029) and platelet mass, rs= 0.466 (2P= 0.028).Since an increased platelet volume is associated with platelet hyperactivity, the increased platelet volume in APKD may be a marker, or even contribute to the development, of premature vascular disease and sudden cardiac death in patients with APKD.