Small vessel disease (SVD) is associated with traditional vascular risk factors (RF). The aim of our study was to determine whether different SVD types, single lacunar infarction (LI) and multiple LI (MLI) with or without white matter lesions (WML), have different RF profiles. Forty RF parameters were analysed in 201 consecutive patients with magnetic resonance imaging finding of SVD. History of arterial hypertension, higher systolic and mean blood pressure (BP) but also hypotension, and higher plasma homocysteine levels were more frequent in MLI compared to single LI patients (p<0.05). Patients with one LI were younger, more frequently had clinically evident stroke and family history of cardiovascular disease (CVD) (p<0.05). Significant difference between groups was found only in these RF, indicating that similar pathological processes led to both types of SVD. Positive correlation with age and family history of CVD necessitates further analyses of other factors, predominantly genetic, as the key to the answer why patients develop different lesions in SVD.