We evaluated the effectiveness of a whole-body bioimpedance device (NICaS®, NI Medical, Petach Tikva, Israel) to predict the presence of a hemodynamically significant patent ductus arteriosus (PDA) in premature infants. A total of 36 infants less than 35 week’s gestation age and birth weights of less than 1750 g were included in the study. Using the NICaS® device, we obtained whole-body bioimpedance measurements of stroke volume index (SI), cardiac output index (CI) and total peripheral resistance index. A total of 61 measurements were taken together with echocardiograph imaging. The study population was divided into three groups according to the echocardiograph results: group 1—small PDA, group 2—moderate PDA, and group 3—large PDA. Both SI and CI significantly increased from a median value of 22.6 ml/m² and 3.4 l/min/m² to 23.8 and 3.7, to 39.8 and 5.4 between groups 1, 2 and 3 respectively. The difference was statistically significant between groups 1 and 3 (P = 0.005 for SI and P = 0.002 for CI) and between groups 2 and 3 (P = 0.037 for SI and P = 0.05 for CI). We found statistically significant differences in SI and CI between infants with large PDAs and infants with no or small and medium PDAs. We suggest that these differences can be used in real time, in addition to echocardiography, in assessing the presence of significant PDAs.