Aims/Hypothesis: Idiopathic sudden sensorineural hearing loss (ISSNHL) represents an acute inner ear disorder with an overall incidence of 5–20/100000 individuals per year in western countries. No clear causes for this disease have been found so far, but cochlear ischemia has been hypothesized as one of the etiopathological mechanisms. The aim of our study was to assess the role of diabetes and traditional cardiovascular risk factors in the pathogenesis of ISSNHL. Materials/Methods: Case-control study of 141 patients (75 males/66 females) matched for age and gender. Cases were affected by ISSNHL, defined as a sudden hearing loss ≧30 dB, within 3 frequencies, developing over 72 h. The control group was composed of 271 sex- and age-matched subjects (142 males/129 females) who agreed to participate in this observational study and provided blood samples for laboratory investigations. Cardiovascular risk factors examined were: diabetes mellitus, smoking history, hypercholesterolemia, hypertriglyceridemia and hypertension. Results: On the univariate analysis, diabetes prevalence was higher in the ISSNHL group (15.6%) compared to controls (8.5%) (p = 0.03). Also hypercholesterolemia was significantly more frequent in the ISSNHL group compared to the control population. There were no statistically significant differences between the 2 populations concerning other cardiovascular risk factors. The risk of ISSNHL tended to increase as the number of cardiovascular risk factors increased (p for linear trend = 0.018). Conclusions: Our findings suggest that diabetes mellitus, hypercholesterolemia and a high burden of cardiovascular risk factors are associated with the risk of ISSNHL.