Automated red cell collection is now a well-established technology. As with any new method, the risks and benefits must be weighed against older approaches, in this case manual collection. Although widely perceived to be safe, manual collection is associated with a number of potential complications, some of which can be serious, even debilitating. The safety record of 2-RBC and other RBC automated procedures is excellent. Physiologic, cardiovascular, and neurocognitive responses are modest and fall within those seen for manual collection. The long term effects related to erythropoietic response and iron loss are manageable and are similar to the effects of repeated whole blood donation. The collection of whole blood by manual means has been performed for nearly a century and as result the safety of this procedure is assumed. Conversely, the safety of automated collection in general and particularly RBC has had to "prove" itself, primarily because it is much more recent and is a different paradigm. Millions of procedures have been performed using both approaches. The blood donor, the "raw material" which makes hemotherapy possible, is the essential enabler in these processes. This article examines the complications of both manual and automated RBC collection.