Between 2015 and 2017, the US Department of Veterans Affairs and the US Department of Defense developed a clinical practice guideline for rehabilitation of lower limb amputation to address key clinical questions. A multidisciplinary workgroup of US Department of Veterans Affairs and US Department of Defense amputation care subject matter experts was formed, and an extensive literature search was performed which identified 3685 citations published from January 2007 to July 2016. Articles were excluded based on established review criteria resulting in 74 studies being considered as evidence addressing one or more of the identified key issues. The identified literature was evaluated and graded using the National Academies of Science GRADE criteria. Recommendations were formulated after extensive review. Eighteen recommendations were confirmed with four having strong evidence and workgroup confidence in the recommendation. Key recommendations address patient and caregiver education, consideration for the use of rigid and semirigid dressings, consideration for the use of microprocessor knees, and managed lifetime care that includes annual transdisciplinary assessments. In conclusion, this clinical practice guideline used the best available evidence from the past 10 yrs to provide key management recommendations to enhance the quality and consistency of rehabilitation care for persons with lower limb amputation.