Introduction: Multifocal fatty liver infiltrations are not uncommon ultrasonographic finding; they are explained by the presence of aberrant vascular supply independent of the portal circulation or insulin resistance. Aim: To study the significance of this ultrasonographic finding. Methods: A study group (n = 96) with multifocal fatty liver and two control groups: healthy subjects (n = 100) and patients with diffuse fatty liver disease (n = 100) were enrolled. They were tested for fasting blood glucose, lipid profile, transaminases, serum insulin, glycated hemoglobin, Homeostatic Model Assessment of Insulin Resistance, high-sensitivity C-reactive protein and liver stiffness in Fibroscan. Results: Patients with multifocal fatty liver showed a statistically significant higher values of serum transaminases, markers of insulin resistance, high-sensitivity C-reactive protein, and neutrophil lymphocyte ratio (p <0.05). Lipid profile parameters were significantly higher (p <0.05). Mean liver stiffness (9.8 ± 1.2 kPa) and carotid intima media thickness (1.16 ± 0.2 mm) were significantly higher when compared to healthy subjects and patients with diffuse fatty liver disease. Independent predictors of insulin resistance and premature carotid atherosclerosis in patients with multifocal fatty liver disease were: serum gamma-glutamyl transferase (odds ratio 1.69), high-sensitivity C-reactive protein (odds ratio 1.62), uric acid (odds ratio 1.55), very low-density lipoprotein (odds ratio 1.74), total cholesterol/high-density lipoprotein (odds ratio 1.58) and severity of liver stiffness measured by Fibroscan (odds ratio 1.9). Conclusions: Multifocal fatty liver is an aggressive form of nonalcoholic fatty liver disease and should be considered a radiological sign of insulin resistance that needs special attention and management.