Background: The cerebral circulation is maintained on the principle of brain uniqueness cerebral autoregulation. Many factors such as oxygen, carbon dioxide, and blood pressure play a major role in the smooth journey of cerebral circulation. There is no clear marker used to assess the impending mortality in sick neonates. The resistive index (RI) is a measure of pulsatile blood flow, reflecting the resistance to flow caused by microvascular bed. The RI of the cerebral vessels is used to know the amount of blood that is flowing in the brain. Increased cerebral blood flow reduces the RI and decreased flow increases the resistance and the brain stays between the two, and hence, the autoregulation is maintained. When the cerebral autoregulation is lost, the flow in the diastole reverses and helps in the prognostication. Objective and Design: A prospective cohort study was conducted between March 2017 and May 2018 catering to both inborn and outborn neonates at Manipal Hospital, Bengaluru, to determine the importance of reversal of diastolic flow of RI in the middle cerebral artery as a marker of mortality in sick neonates. Subjects and Interventions: We enrolled 22 sick neonates both term and preterm. Normal resistive indices in neonates were taken as 0.6–0.9. Method: The RI was manually assessed in the middle cerebral artery using pulsed-wave Doppler. The mean RI was calculated from the average peak systolic velocity and end-diastolic velocity of at least five sequential stable waveforms. The reversal of diastolic flow in the RI was determined by the retrograde flow of waveform during diastole. Univariate and multivariate analyses were performed to identify prognostic factors for the overall survival, which was depicted using Kaplan–Meier curve.P< 0.05 was considered statistically significant. Results: Neonates who had a reversal of diastolic flow had a poor mean survival of 1.3 h when compared to those patients who did not have a reversal of flow of 133.8 days (hazard ratio [HR] – 4.66; 95.% confidence interval [CI]: 1.250–16.96) which was statistically significant (P = 0.022). Furthermore, birth weight <1000 g had a mean survival of 29 days, whereas birth weight >2500 g had a mean survival of 104 days (HR – 0.96; 95% CI: 0.460–2.032) which also was statistically significant (P < 0.001). Conclusion: As determined by univariate and multivariate analyses, the reversal of diastolic flow in the cerebral artery can strongly be used as a surrogate marker for impending mortality in a sick neonate.