This study evaluates the predictive value of the WIfI (Wound, Ischemia, and foot Infection) classification system and pre-amputation transcutaneous oxygen pressure (TcPO2) measurements in forecasting post-amputation complications in major lower limb amputations (MLLA). A retrospective analysis was conducted on 132 MLLA patients with complete WIfI data and 87 patients with documented TcPO2 values. Associations between WIfI stage, TcPO2, and post-amputation outcomes—including healing time, surgical revisions, re-amputation, and wound complications—were assessed using statistical modeling and receiver operating characteristic (ROC) curve analyses. Higher WIfI stages correlated with prolonged healing (WIfI 4 failure rate: 12.8%) but did not significantly predict complications. Unexpectedly, WIfI 2 patients had a 4.4-fold higher risk of revision (p = 0.011) and a 3.1-fold higher re-amputation risk (p = 0.033) compared to WIfI 4. TcPO2 levels showed a significant relationship with healing outcomes, with a 36.9% failure rate in TcPO2 < 15 mmHg. A TcPO2 cut-off of > 46 mmHg optimized healing prediction (HR = 2.81, p = 0.004). TcPO2 is a stronger predictor of post-amputation complications than WIfI staging. A cut-off of > 46 mmHg at the amputation site is recommended to improve healing outcomes.