Iloprost, which has efficacy in the microvascular space, is shown to have beneficial effects on the kidney, which has an extensive microvascular network. We aimed to evaluate the effect of iloprost treatment on kidney functions in patients with critical limb ischemia. Forty-eight patients with critical limb ischemia who were not suitable for revascularization and who were treated with iloprost were evaluated prospectively in our clinic between September 2010 and December 2012. The patients were divided into 2 groups as patients with chronic renal dysfunction (Group I) and patients with normal renal function (Group II). Urine albumin:creatinine ratio and glomerular filtration rate (GFR) calculated using serum creatinine and serum cystatin C (GFRcyc) were used to establish the presence of renal dysfunction. The decrease analgesic requirement, walking distance, reduction in ulcer diameter, the increase in ankle-brachial index, and changes in The Society of Vascular Surgery/International Society of Cardiovascular Surgery criteria were used in the evaluation of treatment response. Opioid analgesic requirement and decubitus pain disappeared after treatment in 58.3% (n = 28) of subjects. Walking distance increased in 66.6% (n = 32). Iloprost treatment significantly increased ankle-brachial index (P < 0.01). In Group I the levels of serum urea, creatinine, and cystatin C significantly decreased (P < 0.05), whereas GFRcyc and GFR calculated using the equation of the Chronic Kidney Disease Epidemiology Collaboration (ie, GFR expressed for specified race, sex, and serum creatinine in milligrams per deciliter) was increased significantly compared with pretreatment levels (P < 0.05). No significant change was observed in urine albumin:creatinine ratio (P > 0.05). The use of iloprost in critical limb ischemia can slow down the progress of early stage renal damage. GFRcyc and cystatin C, which are indicators of early stage chronic renal dysfunction, can be used for the evaluation of treatment response.