Our institution has reported on delayed hemolytic transfusion reaction (DHTR) and delayed serologic transfusion reaction (DSTR) incidence changes. From January 1993 to June 2003, a polyethylene glycol (PEG) tube-based technique was used for red blood cell (RBC) antibody screen. In June 2003, a gel microcolumn technique was implemented. Impact of this on antibody detection and DHTR and DSTR incidence was investigated. Positive antibody screen frequency and antibody specificity from January 2002 to March 2003 and July 2003 to September 2004 were compared. Overall incidence of DHTR and DSTR as well as the number and identity of the RBC antibodies implicated from August 1999 through June 2003 (PEG) and July 2003 through July 2007 (gel) were compared. The mean length of hospital stay (LOS) and number of RBC units transfused per patient were compared. Equivalent numbers of antibody screens were performed with equivalent numbers of positive screens. Significant differences were not seen in the detection of clinically significant antibodies but significantly fewer clinically insignificant antibodies were detected with gel. Ninety-six DHTRs and DSTRs were diagnosed. The LOS and number of transfused RBC units were not statistically different. A significantly higher incidence of DHTRs and DSTRs was seen with PEG compared to the gel. The gel microcolumn method is similar to the PEG in detecting clinically significant antibodies but detects fewer clinically insignificant antibodies. The implementation of gel resulted in a lower incidence of DHTRs and DSTRs compared to PEG.