Background: Blood viscosity is a strong predictor of cardiovascular events. However, the relationship between blood viscosity and acute arterial occlusion (AAO) has not been studied adequately so far. Objectives: The aim of the present study was to assess the relationship between whole blood viscosity (WBV) and AAO. Material and methods: The study included 93 patients who were diagnosed with AAO between January 2017 and September 2019, and 90 age- and sex-matched healthy controls. WBV was assessed using a validated calculation formula derived from hematocrit and total plasma protein levels, both as a low (LSR) and a high (HSR) shear rate. Results: There were no significant differences between the two groups in regards to the baseline characteristics, with the exception of smoking and LDL cholesterol levels. Subjects with AAO presented significantly higher WBV values both at LSR (32.2 ± 5.0 vs. 26.6 ± 5.0, p <0.001) and HSR (6.2 ± 0.3 vs. 5.7 ± 0.3, p <0.001). The ROC analysis revealed a cut-off value of 27.4 for WBV at LSR (sensitivity 66%, specificity 64%, AUC = 0.770, p <0.001) and a cut-off value of 5.29 in case of HSR (sensitivity 69%, specificity 74%, AUC = 0.801, p <0.001) for predicting AAO. Multivariate analysis, both LSR (OR 3.33, 95% CI: 1.20–9.43, p = 0.006) and HSR (p = 0.020, OR: 1.70, 95% CI: 1.020–1.123) were independent predictors of AAO. Conclusions: This study demonstrated that WBV levels at both HSR and LSR are significantly higher in the AAO group than in the control subjects, indicating that an increased WBV may be associated with the development of AAO.