BACKGROUND To evaluate the benefit of methylene blue as an adjunct treatment by assessing hemodynamic, morbidity rate, intensive care unit length of stay, and mortality rate outcomes in adult patients with vasoplegic syndrome. METHODS A systematic search through electronic databases including Pubmed, Embase, Scopus, and Medline for studies assessing the use of methylene blue in patients with vasoplegic syndrome compared to control treatments. The Newcastle-Ottawa Scale tool was used for observational studies, and Jadad Scale was used for controlled trials to assess the risk of bias. RESULTS This systematic review included six studies for qualitative synthesis and five studies for quantitative synthesis. Pooled analysis revealed that mean arterial pressure, systemic vascular resistance, heart rate, and hospital stay were not statistically significant in methylene blue administration compared to control. However, administration of methylene blue in vasoplegic syndrome patients significantly reduces renal failure (OR = 0.25; 95% CI = 0.08-0.75), development of multiple organ failure (OR = 0.09; 95% CI = 0.02-0.51), and mortality rate (OR = 0.12; 95% CI = 0.03-0.46). CONCLUSIONS Adjunct administration of methylene blue for vasoplegic syndrome patients significantly reduces renal failure, multiple organ failure, and mortality.