Injection drug use has devastating effects on the veins, skin, muscles, and joints of the lower extremities, thus increasing the risk of chronic venous disease (CVD). We examined the following risk factors for CVD in persons who injected drugs: health and drug use history, ankle mobility, pain, and skin and wound assessment. Because of deep venous thrombosis and injury and immobility to the calf muscle pump from injected drugs, CVD occurs at a young age. Decreased ankle joint movement, decreased walking, and increased pain are associated with worsening CVD clinical classification. Associated venous ulcers tend to be multiple and large by the time wound care is sought. Cellulitis and abscesses may also be present. Injection drug users serve as a model for the multifactorial nature of CVD including vein damage, diminished ankle range of motion, and decreased calf muscle strength. Persons who inject drugs need to have their lower extremities assessed for CVD on a routine basis.