Background In autosomal dominant polycystic kidney disease (ADPKD), endothelial dysfunction (ED) is common and occurs much earlier than kidney function impairment. The impact of smoking on ED in ADPKD patients has not been previously studied. The aim of this study was to investigate the potential contribution of smoking habits to ED and subclinical atherosclerosis in these patients. Methods This case-control study included 54 ADPKD patients with preserved renal function and 45 healthy control subjects. ED was assessed using ischemia-induced forearm flow-mediated dilatation (FMD). Carotid intima-media thickness (CIMT) was measured from 10 mm proximal to the right common carotid artery. Clinical demographic characteristics and laboratory data were recorded for the patients and control group. Regression analysis was used to determine independent associations of ED and CIMT. Results FMD was significantly lower in the ADPKD patients (19.5 +/- 5.63 vs. 16.56 +/- 6.41, p = .018). Compared with nonsmoker ADPKD patients, smoker patients had significantly lower FMD values (18.19 +/- 6.52 vs. 13.79 +/- 5.27, p = .013). In multiple regression analysis, age (beta = -0.294, 95% CI: -0.392: -1.96, p = .001) for FMD and smoking (beta = 1.328, 95% CI: 0.251, 2.404, p = .017) for CIMT were independent predictors. Conclusions Patients with ADPKD had more impaired endothelial function and subclinical atherosclerosis compared with control subjects. Smoking may increase the risk of subclinical atherosclerosis in ADPKD patients.