In our aging population, primary major amputations (AMP, below-knee or above-knee) continue to be performed despite advances in revascularization. We hypothesized that not only patient comorbidities but also the system of health-care delivery affected the treatment of patients with critical limb ischemia (CLI). A prospective analysis of patients presenting with CLI was undertaken to determine whether patient-specific factors or healthcare delivery factors (system-related) influenced treatment with primary AMP versus lower extremity revascularization (LER). The patient-specific factors age, gender, race/ethnicity, presence of coronary artery disease, cerebrovascular disease, tobacco use, diabetes mellitus (DM), dialysis dependence (end-stage renal disease, ESRD), hypertension, hyperlipidemia, stage of CLI (rest pain, minor or major tissue loss), history of revascularization, and functional status (living situation and ambulatory status) were recorded. The system-related factors time from onset of CLI to vascular surgery evaluation and type of insurance (managed care/other insurance) were also noted. The influence of patient-specific and system-related factors on the primary treatment modality (AMP versus LER) was determined with univariate and multivariate analyses. A total of 224 patients presented with CLI between March 1, 2001, and March 1, 2005. Patients were treated with primary major AMP in 97 cases (43%) and revascularization in 127 cases (57%). On univariate analysis, nonwhite race/ethnicity, DM, ESRD, major tissue loss, dependent living situation, and nonambulatory status were all significant predictors of AMP versus LER (all P < 0.01). On multivariate analysis, major tissue loss, ESRD, DM, and nonambulatory status remained independent predictors of AMP versus LER (all P < 0.05). The system-related factors of time to vascular surgery evaluation (mean 8.6 weeks, 7.1 vs. 9.3 weeks AMP versus LER, P = 0.60) and type of insurance (managed care, 17% vs. 24% AMP vs. LER, P = 0.15) had no influence on treatment. Fifty-four percent of all primary major AMPs were performed due to extensive gangrene or infection present at initial vascular evaluation which precluded limb salvage. Major tissue loss, ESRD, DM, and nonambulatory status are all independent predictors of treatment with primary AMP as opposed to revascularization. Treatment of CLI is determined by patient-specific factors and does not appear to be adversely influenced by system-related factors. Efforts toward improving limb salvage may be best directed at aggressive treatment of medical comorbidities to prevent the late complications of CLI. Earlier recognition of tissue loss and referral to the vascular specialist may lead to improved limb salvage.