Background <p>Paraquat is a herbicide used for weed control and is one of the lethal poisons associated with high mortality. Exposure to this compound could be accidental or as a deliberate self-harm. Clinical manifestations can range from mild symptoms initially to multiorgan failure. Owing to high case fatality (50–90%) and no specific antidote is available; different treatment regimens are proposed with variable success rates. Here, we present two patients with paraquat poisoning, their initial presentation, clinical progress, and successful management.</p> Case presentation <p>Two young adults, one 29-year-old male and one 32-year-old female patient from South India, presented with gastrointestinal symptoms and worsening renal and Liver failure. Patients had already received gastric lavage at the local hospital and later transferred to our hospital. We initiated immunosuppressive therapy with cyclophosphamide at 15&#xa0;mg/kg/day for 3&#xa0;days and steroids. Both patients received renal replacement therapy and N-acetyl cysteine infusion. We observed improvement in clinical and biochemical parameters over a week. There were no respiratory symptoms throughout the hospitalization. At the time of discharge, both patients were off renal replacement therapy. On long-term follow-up after 2.5&#xa0;years, both patients had recovered well without any renal dysfunction.</p> Conclusion <p>This case report highlights the successful management of paraquat poisoning with high-dose cyclophosphamide with steroids. The timely initiation of immunosuppression prevented disease progression and facilitated prompt recovery.</p>