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Background: Polycythemia is the most common adverse effect of testosterone replacement therapy (TRT) and may predispose patients to adverse vascular events. Current Canadian guidelines recommend regular laboratory monitoring and discontinuing TRT or reducing the dose if the hematocrit exceeds 54% (hemoglobin ≥180 g/L). This threshold has been interpreted by some physicians and patients to indicate the need for phlebotomy or blood donation while on TRT., Study Design and Methods: We reviewed all male blood donors in Southwestern Ontario at Canadian Blood Services from December 2013 to March 2016 who self-identified or were found on donor screening to be on TRT. Hemoglobin concentration was measured at the time of donation or clinic visit and with each subsequent appointment in repeat donors., Results: We identified 39 patients on TRT who presented for blood donation over a 2-year period. The mean hemoglobin level at all clinic visits was 173 g/L (range, 134-205 g/L; n = 108). Hemoglobin concentrations of 180 g/L or more (calculated hematocrit, ≥54%) were measured at 25% of appointments. Of the 27 repeat donors, 12 (44%) had persistently elevated hemoglobin levels (≥180 g/L) at subsequent donations., Conclusion: Hemoglobin concentrations were elevated in donors on TRT, and significant numbers had hemoglobin levels above those recommended by current guidelines. These data also suggest that repeat blood donation was insufficient to maintain a hematocrit below 54%. Our findings raise concerns about the persistent risk of vascular events in these donors, particularly when coupled with the misperception by patients and health care providers that donation has reduced or eliminated the risks of TRT-induced polycythemia., (© 2017 AABB.)