BACKGROUND: This study aimed to assess the influence of early administration of methylene blue (MB) and vasopressin on the dose of noradrenaline required to manage septic shock. MATERIALS AND METHODS: This study was a parallel, randomized, controlled trial including 74 adult patients with septic shock admitted to the intensive care unit (ICU). Once the noradrenaline requirement exceeded 0.2 µg/kg/min, patients were randomly allotted to group M and group V. Group M received an intravenous 1 mg/kg bolus of MB over 30 minutes, then an infusion of 0.5 mg/kg over 6 hours. Group V received intravenous vasopressin at a rate of 0.04 units/min for 6 hours. The primary outcome of this research was the dose of noradrenaline required to reach the target mean arterial pressure (MAP) of ≥ 65 mm Hg at 6, 12, and 24 hours. Secondary outcomes included changes in lactate levels, urine output, and sequential organ failure assessment (SOFA) score. RESULTS: The M group required a higher dose of noradrenaline compared with the V group to maintain MAP above the target level at 12 and 24 hours. There had been no significant variation in lactate levels along with SOFA scores between the two groups at earlier time points. However, at 24 hours, the M group had higher lactate levels and SOFA scores than the V group. The V group also showed improvements in urine output at 24 hours compared with the M group. CONCLUSION: Early administration of vasopressin compared with MB was associated with a reduced dose of noradrenaline required for maintaining target MAP in patients presenting with septic shock. HOW TO CITE THIS ARTICLE: Kuri HR, Sharma A, Meshram T, Kothari N, Goyal S, Paliwal B,