The impact of patent ductus arteriosus (PDA) on vital sign trends represented as histograms, and perfusion index in particular, is unknown. This study aimed to split continuously obtained PI andother vital signs before, during, and after medical treatment of PDA, into histogram bins, and determine the utility of PI and other vital sign histograms in the early prediction of hemodynamically significant PDA (hsPDA). In 34 infants at a mean gestational age of 26 ± 2.1 weeks, we prospectively collected vital signs for three different periods, 24 h before starting treatment of PDA, during PDA treatment, and 24 h after completion of the course of treatment, and confirmed PDA closure by echo. Histograms with three comparable periods were obtained from preterm infants who did not require treatment for PDA and analyzed for comparison. The duration of time spent in each histogram bin was determined for each time epoch. Episodes of low PI < 0.4 and high PI > 2 were significantly longer in duration in infants with PDA before treatment compared to those in infants with PDA during and after treatment. The arterial oxygen saturation (SpO2) < 80% was also longer in duration in infants with PDA before compared to that in infants with PDA during and after treatment. Low PI < 0.4 correlated with most echocardiography indices of hsPDA.Conclusion: We conclude that a patent ductus arteriosus requiring treatment in preterm infants ≤ 29 weeks GA was associated with significant fluctuations between a low PI < 0.4 alternating with a high PI > 2, reflecting the dynamic nature of hsPDA shunt volume. PI variability may be an early marker of hsPDA. What is Known: • The perfusion index is a continuous underutilized parameter provided by pulse oximetry to assess the peripheral perfusion. • The perfusion index helps predict conditions with hemodynamic instability. What is New: • The perfusion index assessed as daily histogram trends can predict patent ductus arteriosus requiring treatment.