Atypical antibody detection in DiaMed microtubes using a low‐ionic‐strength saline (LISS) indirect antiglobulin technique (IAT) was assessed using both serum and plasma. During the first period of the study all atypical antibodies originally detected in serum were also detected in EDTA plasma with comparable reaction strengths. Two of 73 antibodies were not detected in citrated plasma.  During the second period of the study all routine antibody screens were performed in both serum and EDTA plasma. More clinically significant antibodies were detected in EDTA plasma than in serum. More false positives and non‐specific antibodies were also detected in EDTA plasma. It is concluded that EDTA plasma is a suitable medium for antibody detection using LISS IAT in DiaMed gel mic