Aim: Peripheral blood mononuclear cell (PB-MNC) therapy is an adjuvant treatment for patients with diabetic foot ulcers (DFUs) and no-option critical limb ischaemia (NO-CLI). The aim of this study was to evaluate the factors influencing the effectiveness of PB-MNC. Method: The study is a prospective, noncontrolled study including patients with DFUs and NO-CLI treated with PB-MNC therapy. NO-CLI was defined by revascularization failure with desert foot (absence of any artery below-the-ankle) or partial desert foot (absence of wound related artery with TcPO2<30 mmHg). Patients were divided in 2 groups: amputees and not amputees after 1 year of follow-up. Clinical, wounds and vascular features were recorded and compared between the 2 groups. Then, factors influencing the clinical response to the PB-MNC were evaluated. Results: Sixty-four patients were included. The mean age was 73.8+/-5.8, all patients had type 2 diabetes, 75% were male, 81% showed infected DFUs, 93.7% had a gangrene. Survival with limb salvage was recorded in 75% of cases, major amputation in 12.5% and mortality in 12.5%. Amputees in comparison to not amputees had a higher rate of desert foot (100% vs 25%, p<0.0001), higher post-procedural pain (5.7+/-1.9 vs 2.2+/-1.3, p<0.0001), lower TcPO2 values after PB-MNC (30+/-8 vs 43+/-8 mmHg, p 0.0001) and higher rate of heel DFUs (75% vs 21.4%, p 0.002). The presence of desert foot before PB-MNC, heel DFUs and the persistence of post-procedural pain were independent predictors of major amputation Conclusion: The current study showed that PB-MNC therapy resulted less effective in patients who had pre-procedural desert foot, heel ulcers and the persistence of post-procedural pain.