Objective: To provide a solid baseline reference for quality of life (QoL) in patients with no-option critical limb ischemia (CLI). CLI is associated with surgery, endovascular interventions, hospitalization, and a poor prognosis. An increasing number of clinical trials are, therefore, investigating new treatment strategies (eg, therapeutic neovascularization) in patients with CLI. QoL serves as an important secondary endpoint in many of these trials, but solid reference QoL data for patients with no-option CLI are lacking. Methods: The Medical Outcomes Study Short Form 36 (SF-36) and the EuroQol-5D (EQ-5D) questionnaires were used to obtain baseline QoL scores from 47 patients with no-option CLI participating in a therapeutic neovascularization trial. To allow for easy comparability, a norm-based scoring (NBS) method was used to report the results of the SF-36. Scores of patients with CLI were furthermore compared with scores of patients with milder forms of peripheral arterial disease (PAD) and with patients with cardiovascular risk factors only. Determinants of QoL in patients with PAD were identified using multiple linear regression methods. Results: Patients with no-option CLI reported QoL scores below the general population mean on every health dimension of the SF-36. Physical functioning, role physical functioning, and bodily pain were affected most intensively. These poor physical QoL scores were further underlined when compared with other patients with milder forms of PAD or patients with cardiovascular risk factors only. Patients with CLI scored poorly on the pain/discomfort and the usual activities domain of the EQ-5D. Diabetes, female gender, body mass index, and the ankle-brachial index at rest were significant determinants of the QoL in PAD on multivariate analysis. Conclusion: The QoL data of patients with no-option CLI using NBS methods for the SF-36 provide a baseline reference for ongoing clinical trials on new treatment strategies. Our data stress the need for new revascularization therapies in patients with no-option CLI.