Despite a meticulous multidisciplinary team approach, limb salvage remains uncertain even after the initial forefoot amputation in patients with end-stage diabetes. Which of many factors strongly influence the early failure of the limb salvage strategy remains unknown. This study aimed to analyze perioperative independent risk factors for major amputation within 1 year following first-time diabetic forefoot amputation. Perioperative variables of 808 diabetic forefoot amputations performed in a tertiary referral center specialized for organ transplantation and end-stage diabetes were analyzed. Major amputations were performed in 104 patients (12.9%) throughout follow-up, and 77 (74%) of 104 patients had their major amputation within 1 year. Cox proportional hazards were examined to assess the risk factors for major amputation performed within 1 year. In univariate analysis, 18 possible risk factors significantly differed between patients with and without early major amputation. In stepwise multivariable analysis, chronic renal failure (CRF), peritoneal dialysis, and bilateral initial amputation were strong risk factors for early major amputation, with hazard ratios of 2.973 (95% CI 1.805-4.896, P < .0001), 2.558 (95% CI 1.113-5.881, P = .027), and 2.515 (95% CI 1.318-4.798, P = .005), respectively. Regardless of kidney transplantation (KT) status, CRF strongly predicts >20% chance of major amputation within 1 year after the first diabetic forefoot amputation.