The literature on the use of therapeutic apheresis is often criticized for the preponderance of low to very low quality evidence. Shehata et al. examined the apheresis literature published between 1976 and 1999 and found a lack of randomized controlled trials with those identified demonstrating significant limitations. To determine if this has improved, MEDLINE was searched for randomized controlled therapeutic apheresis trials. In addition, the Clinicaltrials.gov database was also searched for actively recruiting randomized controlled therapeutic apheresis trials. The results revealed that the total and average number of publications per year examining therapeutic apheresis has increased substantially in the period 2000–2012 compared to 1976–1999. This was associated with a small increase in the average number of randomized controlled trials reported each year, but these trials represented a smaller percentage of the therapeutic apheresis literature published compared to the 1976–1999 time range. The reported trials continued to have very small numbers of enrolled patients raising questions about their ability to determine whether apheresis represents an effective therapy. Finally, according to the Clinicaltrials.gov database, a small number of randomized controlled trials of therapeutic apheresis are enrolling patients. Despite an increasing emphasis on evidence-based medicine and the need for quality randomized controlled clinical trials, there is still a lack of such trials when it comes to therapeutic apheresis. There continues to be a need for more and better designed randomized trials in therapeutic apheresis. J. Clin. Apheresis 28:48–55, 2013. © 2013 Wiley Periodicals, Inc.