Introduction. Plasma chitotriosidase (ChT) activity is associated with the presence of atherosclerosis and is a new cardiovascular risk marker. Although available evidence supports its role in atherogenesis, there is a lack of an obvious correlation between plasma ChT activity and erectile dysfunction (ED). Aim. Our aim was to investigate the association of the level of serum ChT activity with ED. Main Outcome Measures. Erectile function was assessed using Sexual Health Inventory for Men (SHIM). Serum fasting lipid profile (plasma total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol, and triglycerides); sex hormones (luteinizing hormone, follicle-stimulating hormone, prolactin, total testosterone, and estradiol); and thyroid-stimulating hormone were measured. Plasma ChT activity, as well as K(m), V(max), optimum pH, and heat stability of the ChT were also assessed. Penile duplex ultrasound examination before and after intracavernous injection of 20 microg prostaglandin E1 (PGE(1)), pudendal nerve conduction tests and sensory-evoked potential studies were done to identify patients with arteriogenic ED. Intima-media thickness (IMT) and plaque formation of common carotid artery were determined bilaterally using B-mode ultrasonography. Methods. A total of 124 normolipidemic patients with ED and 120 healthy controls were recruited for this study. Results. Serum ChT activity in patients with ED (116 +/- 18 nmol/h/mL) was significantly higher than in normal control subjects (51 +/- 12 nmol/h/mL) (P < 0.001). There was a significant positive correlation between plasma ChT activity and (i) severity of ED and (ii) duration of ED (r = 0.68, P = 0.004; and r = 0.62, P = 0.01 respectively).We also found that all ChT kinetic parameters assessed (K(m), V(max), and optimum pH) in plasma of ED patients were significantly different from those of normal controls (all P < 0.001). The results of heat stability analysis, demonstrated that plasma ChT activity in the normal individuals was more stable than in the patients with arteriogenic ED (P < 0.001). A significant correlation was seen between the plasma ChT activity and the mean common carotid IMT (r = 0.78, P = 0.002). Moreover, a significant correlation was seen between the severity of ED and mean common carotid IMT (r = 0.74, P = 0.003). We did not address chitotriosidase genotype. Conclusions. Our results indicate that plasma ChT activity is increased in normolipidemic patients with arteriogenic ED, suggesting its possible role in the pathophysiology of arteriogenic ED. The clinical significance of this increase should be assessed in further studies. Safarinejad MR, and Safarinejad SH. Plasma chitotriosidase activity and arteriogenic erectile dysfunction: Association with the presence, severity, and duration. J Sex Med **;**:**-**.