OBJECTIVE: Low/middle-income countries face a disproportionate burden of cardiovascular diseases. However, among cardiovascular diseases, burden of and associations with lower extremity disease (LED) (peripheral arterial disease and/or neuropathy) is neglected. We investigated the prevalence and factors associated with LED among individuals known to have cardiovascular disease risk factors (CVDRFs) in Malawi, a low-income country with a significant prevalence of CVDRFs. DESIGN: This was a stratified cross-sectional study. SETTING: This study was conducted in urban Lilongwe Area 25, and the rural Karonga Health and Demographic Surveillance Site. PARTICIPANTS: Participants were at least 18 years old and had been identified to have two or more known CVDRFs. MAIN OUTCOME MEASURES: LED-determined by the presence of one of the following: neuropathy (as assessed by a 10 g monofilament), arterial disease (absent peripheral pulses, claudication as assessed by the Edinburgh claudication questionnaire or Ankle Brachial Pulse Index (ABPI) <0.9), previous amputation or ulceration of the lower limbs. RESULTS: There were 806 individuals enrolled into the study. Mean age was 52.5 years; 53.5% of participants were men (n=431) and 56.7% (n=457) were from the rural site. Nearly a quarter (24.1%; 95% CI: 21.2 to 27.2) of the participants had at least one symptom or sign of LED. 12.8% had neuropathy, 6.7% had absent pulses, 10.0% had claudication, 1.9% had ABPI <0.9, 0.9% had an amputation and 1.1% had lower limb ulcers. LED had statistically significant association with increasing age, urban residence and use of indoor fires. CONCLUSIONS: This study demonstrated that a quarter of individuals with two or more CVDRFs have evidence of LED and 2.4% have an amputation or signs of limb threatening ulceration or amputation. Further epidemiological and health systems research is warranted to prevent LED and limb loss.