Purpose: This study was performed to determine the natural history of patients with symptoms of claudication and systolic toe pressures (TP) of 40 mm Hg or less. Methods: We followed the clinical course of 56 men with stable claudication and TP of 40 mm Hg or less. All TP measurements were performed on at least two occasions 6 months apart. Primary end points included development of rest pain, tissue loss, or gangrene. The clinical course of 56 case controls with TP greater than 40 mm Hg matched for age, sex, and race was used for comparison. Results: During a mean (± SD) follow-up time of 31 ± 4 months, 37 (66%) patients with TP of 40 mm Hg or less remained stable, and 19 (34%) had ulceration (n = 10), rest pain (n = 6), or gangrene (n = 3). Nine (24%) of the 37 stable patients had gradual improvement of TP values greater than 40 mm Hg. Among the 19 patients whose conditions deteriorated, eight (42%) patients underwent successful bypasses, and five (26%) patients required amputations. Two patients who had rest pain had spontaneous resolution, and three patients who had ulcerations healed without intervention. In contrast, five (9%) of the case controls with TP greater than 40 mm Hg had rest pain (n = 2) or gangrene (n = 3) (p = 0.003). Among patients with TP of 40 mm Hg or less, there were no statistically significant differences between the stable patients and patients with deteriorating conditions in age, ankle-brachial indexes, or risk factors (including diabetes mellitus). However, diabetes conferred a higher probability of clinical deterioration (p = 0.005, Kaplan-Meier). Conclusions: In patients with symptoms of intermittent claudication, TP of 40 mm Hg or less portends clinical deterioration. Patients with diabetes in this group have a significantly higher risk of development of critical ischemia. Close scrutiny is warranted.