Thromboangiitis obliterans (TAO) is a rare, tobacco-associated vasculitis that primarily affects the distal extremities of young males. In advanced stages, it often leads to chronic limb ischemia with ischemic ulceration, culminating in amputation. Data on risk factors for reamputation in this population remain limited. This study aimed to identify clinical, radiological and microbiological predictors of reamputation in patients with TAO-related foot ulcers undergoing amputation. A retrospective cohort study was conducted on 25 patients (31 limbs) with Fontaine stage IV TAO ulcers who underwent lower extremity amputation between January 2021 and December 2024. Patients were stratified into two groups based on whether they underwent repeat amputation (Group 1) or a single procedure (Group 2). Preoperative magnetic resonance imaging, intraoperative tissue cultures and laboratory data were evaluated. Smoking status, hospitalisation metrics and adjunctive therapies were recorded. Statistical analysis included Mann–Whitney U, Fisher's exact test, ROC curve analysis and multivariate logistic regression. Seventeen limbs required reamputation. Persistent smoking was observed in 100% of Group 1 compared with 58.4% of Group 2 (p = 0.015). Positive intraoperative cultures were significantly more frequent in Group 1 (64.7% vs. 21.4%; p = 0.029), with all multidrug-resistant organisms confined to this group. Length of hospital stay was significantly longer in Group 1 (25.2 ± 6.4 vs. 15.8 ± 5.3 days; p = 0.001). ROC analysis identified > 19 days of hospitalisation as a threshold for reamputation risk (AUC = 0.781; p = 0.018). Multivariate analysis identified three independent predictors of reamputation: persistent smoking (OR: 5.2, 95% CI: 1.2–22.8; p = 0.015), positive intraoperative culture (OR: 4.7, 95% CI: 1.1–20.1; p = 0.041), and hospitalisation longer than 19 days (OR: 6.5, 95% CI: 1.4–29.4; p = 0.018). Reamputation in advanced-stage TAO is strongly associated with modifiable factors, particularly ongoing tobacco use, Gram-negative infection and prolonged hospital stay. Early identification and targeted intervention addressing these variables may improve limb preservation outcomes in this high-risk population.