Yellow phosphorus containing rat killer paste causes toxic hepatitis and coagulopathy in humans. It is a common mode of self-harm in a developing country like India. Till date, only liver transplant is the definitive treatment of fulminant liver failure caused by rat killer paste poison. Plasmapheresis replaces the main functions of the failing liver and removes proinflammatory cytokines that are responsible for multi-organ failure. The replacement fluid replenishes the coagulation factors, albumin and immunoglobulins. The complete process improves the microenvironment of the liver, which in turn accelerates the regeneration and helps in the functional recovery. In this study, we have tried plasmapheresis as an innovative approach for the management of liver failure cases due to rat killer paste poisoning. This prospective study was conducted in Madurai Medical College. The dialysis machine used was 4008 S Fresenius and the filter used was Plasma Flux P2 filter. 76 cases (Male-47, Female-29) with a definite history of rat killer paste poisoning who had INR more than 3, hepatic encephalopathy and 10-fold elevation in the liver enzymes were taken up for plasmapheresis and the outcomes compared. Pre and post plasmapheresis liver function tests (LFTs) and coagulation profile were compared, and Model for End stage Liver Disease (MELD) score was calculated. Delta MELD was calculated as the difference between pre and post plasmapheresis MELD score. The population was subjected to a minimum of 1 session and a maximum of 3 sessions of plasmapheresis. The replacement fluid was Fresh Frozen Plasma (FFP) according to the body weight. All the patients were also treated with iv glutathione and N-Acetyl cysteine. The median age was 23 years (19-32) (Median with Interquartile Range). The overall survival rate was 63.2 %. 88.2 % of the population had hyponatremia (survivors- 131.5 mEq/L, non-survivors- 129.57 mEq/L), which was found to be statistically significant with regards to outcome (p <0.001). Incidence of hypokalemia, leucopenia and thrombocytopenia were 51.3%, 52.6% and 47.4% respectively, though not statistically significant. Comparison of the pre and post plasmapheresis LFTs were found to be significant to outcome (p-0.001) [Total Bilirubin (12.4mg/dl, 6.8mg/dl), SGOT (1126 IU/L, 108 IU/L), SGPT (876 IU/L, 116 IU/L), PT (51.1s, 18.4s), INR (4.6, 1.5), APTT (48s, 30.2s)]. Median Delta MELD was found to be 12.08 in survivors, whereas it was 8.7 in non survivors, and was found to be statistically significant with regards to outcome (p- 0.001). The total number of plasmapheresis sessions conducted also correlated with outcome (p-0.001). The Median Survival Time in non-survivors was 199.585 hours (95% Confidence Interval). Plasmapheresis can be a therapeutic option for the treatment for acute liver failure due to rat killer paste poisoning. This is supported by the fact that there is a significant improvement in the liver functions and the coagulation parameters post plasmapheresis. Delta MELD may be used as a prognostic indicator of outcome.