Aim. Patients with end-stage critical limb ischemia (CLI) survive on borrowed time and amputation is inevitable if an aggressive management stratagem is not instigated. Our primary aim was to equate effectiveness of subintimal angioplasty (SIA) and tibial balloon angioplasty (TBA) in sustaining clinical improvement and amputation free survival (AFS) in patients with CLI TASD II D. Moreover, patients with severe CLI, who were not suitable for revascularization and who were offered therapy with a sequential compression biomechanical device (SCBD) were scrutinised as part of a comprehensive lower limb salvage program.Methods. From 2002-2012, 5876 patients were referred with peripheral vascular disease (PVD); 987 presented with CLI and 798 had intervention; 189 patients presenting with CLI were not candidates for revascularisation, out of which 171 were offered SCBD. We formed a prospective observational group study of 441 patient who had TASC D disease. All of these patients presented as emergencies and were allocated to the next available treatment list. Duplex ultrasound arterial mapping (DUAM) was the sole pre-operative investigation tool in 92% of all cases. Of the 441 patients studied, 190 patients (206 procedures) has SIA for TASC D femero-popliteal occlusions, 80 patients (89 procedures) had TBA and cool eximer laser angioplasty (CELA) for tibial artery occlusions and 171 patients with severe CLI were not suitable for revascularization and joined the SCBD program. Mean age (SIA 73 +/- 13 years vs. TBA/CELA 74 +/- 8 years vs. SCBD 75 +/- 13 years), and comorbidity severity scores (P>0.05) were similar between groups.Results. Perioperative mortality within the SIA group was 1.6% vs. 0% within the TBA group and 0.6% in SCBD. Length of hospital stay within the TBA group was 3.8 +/- 2 days vs. SIA 14 +/- 16 days, P<0.0001. The 5-year freedom from major adverse events (MAE) for the SIA group was 68% that was comparable to the results obtained for both the TBA group; 59%, and SCBD group: 62.5% (P=0.1935). Five-year freedom from target lesion revascularization was 85.9% within the SIA group and 79% within the TBA group. A sustained clinical improvement was seen in 82.8% of primary SIA and 68% of TBA, which mimics the outcome of SCBD at 68% at one year. A total of 83% SCBD patients had no rest pain within one week of starting the program and gangrene remained dry and non-progressive. Ulceration healed in all but 12 patients. There were no device-related complications. Limb salvage was 94% at 5 years. All-cause survival was 69%. Quality time spent without symptoms of disease or toxicity of treatment (Q-TWiST) was 24.7 months for SIA and 8.5 months for TBA and was 38.13 for SCBD for a total of 708 months of usage. Cost per quality adjusted-life years (QALY) for SIA was (sic) 5662.79, (sic) 12,935.18 for TBA and (sic) 2943.56 for SCBD.Conclusion. All treatment pathways augmented patient-specific Q-TWiST with substantial cost reduction. SIA, TBA and SCBD expand AFS and symptomfree survival. All treatment modalities are minimally invasive and allow for a high patient turnover without compromising limb salvage, once they are performed by experienced vascular surgeons in high deliberate practice volume centers.