ObjectiveWe aim to compare the effects of pre-existing mood disorders and chronic kidney disease (CKD) on ambulation outcomes for patients who have undergone major lower extremity amputation (MLEA) while also stratifying by the presence of social factors.MethodsWe performed a retrospective chart review of 700 patients admitted from 2014 to 2022 who underwent MLEA. We performed Chi-square tests and binomial logistic regression with p < 0.05 as our significance level.ResultsMood disorder patients have higher rates of independent ambulation if they have familial support (p = 0.022), a listed primary care provider (PCP; p = 0.013), a six-month follow-up (p < 0.001), or a one-year follow-up (p < 0.001). Patients with a history of mood disorder have significantly decreased odds of prosthesis usage (OR: 0.58, 95% CI: 0.40-0.86) but have higher rates of prosthesis usage if they have familial support (p = 0.002), a PCP listed (p = 0.005), a six-month follow-up (p < 0.001), or a one-year follow-up (p < 0.001). CKD patients have significantly decreased odds of eventual independent ambulation (OR: 0.69, 95% CI: 0.49-0.97) but have significantly increased rates of independent ambulation if they have familial support (p =0.041) and six-month (p < 0.001) or one-year follow-up (p < 0.001). CKD patients only have significant changes in prosthesis usage with a six-month (p < 0.001) or one-year follow-up (p < 0.001).ConclusionsPre-existing CKD and mood disorders are associated with decreased odds of independent ambulation and prosthesis usage, respectively. Social factors such as family support, a listed PCP, and timely follow-up are associated with markedly improved ambulatory outcomes for MLEA patients with mood disorders and CKD, with significantly improved prosthesis usage outcomes in only the mood disorder population.