OBJECTIVE Incomplete circle of Willis (CoW) configuration is an important risk factor for cerebrovascular pathology, namely aneurysm formation and ischemic stroke. This study was performed to characterize CoW variation using digital subtraction angiography and to identify demographic and physiologic features that may influence the risk of having an incomplete CoW configuration. METHODS A retrospective review of 274 patients who underwent cerebral angiography by a single surgeon for any indication was conducted. Each CoW branch was graded as normal, hypoplastic, or aplastic. Univariate and multivariate regression analyses were conducted to assess the impact of age, gender, race, and certain comorbidities on CoW configuration. RESULTS A complete CoW was identified in 37.23% of patients. In univariate analysis, patients <40 years old were more likely to have a complete CoW (odds ratio [OR]: 4.973, 95% confidence interval [CI]: 2.610-9.476, P < 0.001) as were patients <70 years old (OR: 2.849, 95% CI: 1.131-7.194, P < 0.05). Univariate analysis on demographic factors and comorbidities revealed CoW completeness to decrease with hypertension (OR: 0.575, 95% CI: 0.347-0.951, P = 0.031) and diabetes mellitus (OR: 0.368, 95% CI: 0.180-0.754, P = 0.006). Multivariable logistic regression analysis used to assess the impact of age on CoW completeness showed age to be an independent predictor of complete CoW, with an inverse correlation between increasing age and CoW completeness (OR: 0.955, 95% CI: 0.937-0.973, P < 0.001) after controlling for potential confounders including hypertension and diabetes mellitus. CONCLUSIONS CoW configuration shows considerable variation with age; however, further investigation is required to elucidate the full impact of other demographic and vascular risk factors on CoW anatomy.