AbstractThe frequency of anaphylactoid reactions to protamine sulfate was examined by reviewing the records of diabetic patients undergoing cardiac catheterization over a 5‐year period, and by prospectively monitoring diabetic patients receiving NPH insulin during the infusion of protamine sulfate.No anaphylactoid reactions were noted after protamine administration (48 ± 5 mg) in the retrospective study in either patients with prior exposure to protamine (74 catheterizations) or in diabetics with no exposure to protamine (132 catheterizations). In the prospective study, no anaphylactoid reactions were seen in the 24 NPH insulin‐dependent diabetics during the infusion of protamine sulfate (45 ± 5 mg). Five of the 42 patients (12%) from the retrospective study who underwent vascular surgery developed severe reactions to much larger doses of protamine (380 ± 118 mg).Diabetics with prior exposure to protamine sulfate do not appear to be at increased risk of anaphylactoid reaction after the administration of protamine sulfate in the dose range of<50 mg at the time of cardiac catheteri