Purpose Hyperammonemia is a fatal complication post lung transplantation. There are no guidelines for treating hyperammonemia and hence various treatment protocols have been tried. We present a short case series of Hyperammonemia post LTx from India with focusing on Plasmapheresis with Renal Replacement Therapy (RRT) as a combination treatment option apart from routine standard measures leading to survival. Methods We conducted a retrospective study of patients who underwent LTx between April 1 2017 and March 1 , 2020. Patients who developed hyperammonemia syndrome in the post transplantation period, which was defined as symptoms of encephalopathy and plasma ammonia level exceeding 200 μmol/L , excluding hepatic dysfunction were included. Data including demographics, antimicrobial, immunosuppression , ammonia levels , and outcomes were noted. Results 4 of 132 lung transplant recipients developed hyperammonemia syndrome postoperatively during this time period. Median time to peak Ammonia level was 7 days, and median peak ammonia level was 336 μmol/L. All 4 patients were treated with bowel decontamination measures like Metronidazole, Lactulose, Rifaximin . 3 patients received SLED and 1 patient received CRRT. Prompt discontinuation of CNIs was done in all 4 patients. Sodium benzoate infusions were also initiated. 1 patient was also treated with Plasmapheresis with SLED which helped in recovery and survival. Same patient had also received ATG after CNI discontinuation. 3 of the 4 patients died. All 3 patients who expired had poor Tacrolimus Metaboliser status while the patient who recovered had Intermediate Tacrolimus Metaboliser status. Conclusion Hyperammonemia post lung transplantation is often a fatal complication. A multipronged approach is required to achieve survival. Combining Plasmapheresis with SLED /CRRT apart from other standard measures like Bowel decontamination, Prompt discontinuation of CNIs, treating Urease splitting organisms, etc might be an answer to recovery and survival for Hyperammonemia post LTx. Further research is required to determine efficacy of combining Plasmapheresis with RRT along with other treatment options . Also recipient's Tacrolimus Metaboliser status might correlate for developing Hyperammonemia and response to treatment which would warrant further research.