Replantation of amputated limbs after long ischemic hours almost always comes with reperfusion syndrome and poor outcomes. An ischemic time of greater than 6 h is often considered unsuitable for major limb replantation. However, usage of extracorporeal perfusion has been shown to prolong the viability of major limbs in animal studies. The aim of this report is to show that extracorporeal perfusion with cardiopulmonary bypass machine (CPBM) is a safe and reliable technique in improving limb survival as illustrated by our cases. We report two cases of successful major limb replantation with late presentation. One case involved a 31-year-old man with shoulder disarticulation and the other involved a 30-year-old man sustained proximal transtibial amputation. Both patients, who were generally fit, were involved in major road traffic accidents. The amputated segments were connected to a CPBM to expedite reperfusion and to flush away anaerobic metabolic products. The major vessels were cannulated and connected to a bypass machine that was initially primed with heparinized saline and perfused with packed cells at 100% oxygen concentration. The perfusion was carried out at 35°C with low pressure to prevent edema and low flow to reduce reperfusion injury. Venous blood was drained completely before replantation. Total ischemia times were 7 h 40 min and 9 h, respectively. No evidences of perioperative reperfusion syndrome were seen. Both of the replanted limbs survived and patients had regained better-than-expected limb functional outcomes at 5-year and 2-year follow-up, respectively. CPBM may be safely used in major replantation surgery to enhance limb survival and therefore warrants further research.