Lower extremity amputation (LEA) in patients with diabetes results in high mortality, reduced quality of life, and increased medical costs. Exact data on incidences of LEA in diabetic and non-diabetic patients are important for improvements in preventative diabetic foot care, avoidance of fatal outcomes, as well as a solid basis for health policy and the economy. However, published data are conflicting, underlining the necessity for the present systematic review of population-based studies on incidence, relative risks and changes of amputation rates over time. It was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Nineteen out of 1582 studies retrieved were included in the analysis. The incidence of LEA in the diabetic population ranged from 78 to 704 per 100,000 person-years and the relative risks between diabetic and non-diabetic patients varied between 7.4 and 41.3. Study designs, statistical methods, definitions of major and minor amputations, as well as the methods to identify patients with diabetes differed greatly, explaining in part these considerable differences. Some studies found a decrease in incidence of LEA as well as relative risks over time. This obvious lack of evidence should be overcome by new studies using a standardized design with comparable methods and definitions.Systematic review registration numberPROSPERO CRD4201501780