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Background: Low hemoglobin (Hb) levels are a common reason for whole blood donor deferral. As some of the deferred donors do not return to donate blood later, the development of accurate tools to reliably detect low Hb levels is therefore important for donor safety and retention.Study Design and Methods: In a prospective study, 1483 whole blood donors were enrolled in three study arms. In each study arm the Hb results measured with a point-of-care testing device were compared with the venous Hb results obtained in our central laboratory. Both an invasive capillary Hb (Compolab) and a noninvasive spectroscopy Hb (Haemospect) were tested. For the latter, two different application methods for the positioning of the Digiclip were assessed. In a second phase the Compolab was tested in routine conditions.Results: The Haemospect device failed to reliably identify donors with Hb levels below the European cutoffs (125 g/L for females and 135 g/L for males). In contrast, the Compolab identified 72.4% of first-time donors and 78.9% of regular donors with Hb levels below these cutoffs. In routine conditions, the Compolab identified the majority of donors with low Hb levels.Conclusion: Differences between Hb levels measured with invasive and noninvasive point-of-care devices and measured on venous samples exist. Implementing the Compolab at collection sites provides a high level of safety toward first-time donors. [ABSTRACT FROM AUTHOR]