Aim: Our study aimed to evaluate if the presence of anemia may complicate and increase the pathogenetic effect of MDR on clinical outcomes in diabetic foot (DF) patients. Methods: We retrospectively analysed all patients admitted in our Department in 2022 for DF, dividing them in two groups according to presence (Group A) or absence (Group B) of anemia, defined as both total Hemoglobin (HB) and red blood cells (RBC) below 2 SD from normal values corrected for age and sex. We compared groups for clinical, demographic characteristics, blood chemistry, procedures and clinical outcomes: healing rate (HR) and time (HT) and recurrence rate (RR). We compared clinical outcomes between Groups according to the detection of MDR. Results: We derived data of 280 patients: 164 patients in Group A [58.6%; age 70.7±11.2 yrs; male/female 77.4/22.6%; DM1/DM2 6.9/93.1%; Hba1c 57.8±19.1 mmol/mol; diabetes duration (DD) 21.2±12.4 yrs] and 116 in Group B (41.1%; age 71.1±10.7 yrs; male/female 73.2/26.8%; DM1/DM2 8.1/91.9%; Hba1c 59.1±17.2mmol/mol; DD 19.9±13.8 yrs). In the overall cohort Group A showed a lower healing rate (45.7% vs 78.4%, p<0.002), a longer healing time (98±62 days vs 82±54 days, p<0.05) and a higher recurrence rate (29.4% vs 21.2%, p<0.05). When considering separately Staphilococcus Aureus (SA), Pseudomonas Aeruginosa (PA) and Enterobacteriaceae (EN), their relative effect is greater on Group A than on Group B: SA determines a higher reduction in HR (17.5% vs 14.2%, p<0.05) and a greater increase in HT (21±16 vs 9±6 days, p<0.002) and in RR (7.3% vs 3.0%, p<0.002). PA is associated with a higher reduction in HR (8.9% vs 4.7%, p<0.002) and greater increase in RR (6.4% vs 3.3%, p<0.05) and EN with a greater reduction in HR (9.5% vs 4.8%, p<0.02) Conclusions: Anemia and MDR are able to play a synergistic role on clinical outcomes of DF patients worsening healing chances.