Objectives: This study was designed to review the incidence of adverse events during nearly 20,000 apheresis procedures over a 4-year period in a hospital-based program. Methods: Data were obtained from a review of: (1) apheresis adverse event forms (2) hospital or emergency room medical records (3) the databank for donor and procedure-related variables. Adverse events during or after the apheresis procedures were analyzed according to the following categories: (1) complications related to citrate toxicity; (2) hypotensive or vasovagal episodes; (3) complications or symptoms consistent with coronary ischemia; (4) complications related to percutaneous needle insertion, and (5) miscellaneous procedure-related events or nonspecific symptoms. Serious adverse events were categorized as persistent or severe hemodynamic changes as well as other events that required further medical evaluation. Results: Of 19,736 apheresis procedures, 159 (0.81%) were associated with adverse events. In 2376 first-time donations, 26 (1.09%) developed adverse events compared to 133 (0.77%) of 17,360 repeat procedures (p = 0.10). Seventy (0.35%) of 159 donation-related adverse events involved hemodynamic or citrate-related complications and 73 (0.37%) involved venipuncture-related complications, of which 2 required subsequent neurologic consultation. The remaining 23 (0.12%) adverse events involved procedure-related, nonspecific complications. Forty-seven (0.24%) of the 19,736 apheresis procedures were associated with serious adverse events (SAEs). Seven of these serious adverse events required admission to an emergency department, and 2 required hospitalization for further evaluation. Multivariate analysis revealed that apheresis machine model, donor gender and weight, the concomitant harvesting of plasma, the frequency of donation, and citrate-related symptoms (e.g. paresthesias) were independently associated with severe hypotensive reactions. Conclusions: Apheresis procedures have a 150-fold higher incidence of SAEs requiring hospitalization compared to whole blood donation. Identification of donors at risk for complications can facilitate modification of the apheresis procedure in order to reduce the likelihood of adverse events. Although our study did not demonstrate a cause-effect relationship between platelet donation and the development of acute coronary syndromes, underlying cardiovascular disease was detected in 2 donors during or after the apheresis who were otherwise asymptomatic.