Background: The high morbidity and mortality rate in peripheral arterial disease (PAD) is due to the marked tendency for the systemic progression of atherosclerosis. The preconditions for a better prognosis are early identification and early prediction of risk, followed by preventive therapy based on the risk and therapy addressing the cause. Objective: The research aimed to improve the stratification of risk for patients with symptomatic PAD by evaluating new and established indicators and predictors of systemic progression of atherosclerosis. Patients and method: Multilocular quantitative non-invasive characterisation of atherosclerotic vascular disease, based on the indications, was effected in 1207 patients with symptomatic PAD. A range of clinical, vascular, genetic and biohumoral parameters were selected as indicators or predictors of systemic progression of atherosclerosis. The parameters were evaluated in patients with initially isolated PAD in a 24-month monitoring period, in which local and systemic progression was recorded, and they were also evaluated in comparative studies of patients with isolated PAD and patients with additional systemic manifestations of atherosclerosis. Main results: In addition to the ankle brachial blood pressure index, the most important prognostic indicator in PAD, it was able to identify hyperhomocysteinaemia as a crucial predictive marker for systemic progression. Proximal or combined localisation types, combinations of risk factors in the presence of diabetes mellitus, and hyperlipoproteinaemia, microalbuminuria and advanced age are significant predictive indicators of systemic progression. The deletion polymorphism of the ACE gene and the increased intima-media thickness at an early stage of PAD were not found to be of fundamental predictive relevance to systemic progression. A multivariable risk score was produced by bringing together the predictive markers for systemic progression of atherosclerosis, and this makes it possible to grade the risks within a risk stratification framework. Conclusions: Multivariable risk stratification makes it possible to identify the collective maximum risks of early systemic progression of atherosclerosis in PAD. As a result, clinical and preventive strategies can be developed and established for the relevant areas of risk, as can appropriate non-invasive diagnostic methods for monitoring the effectiveness of prevention.