Continuous infusion (CI) of coagulation factor concentrates has been used since the early 1990s. Recent reports of the occurrence of an inhibitor after CI have raised concerns about this method of treatment. We conducted a retrospective study to investigate the development of inhibitors after CI of Factor VIII concentrates in Germany. So far, 13 hemophilia centers have been contacted, and data have been collected by a questionnaire. Of the 13 centers, CI had never been performed in three, no inhibitors had been detected in five, and inhibitor development after CI was recorded in 10 patients in the remaining five centers. Of these 10 patients (ages 7 months to 57 years), five were suffering from severe, one from moderate, and four from mild hemophilia. Indications for treatment were major bleeds and surgical procedures. Plasma-derived (6 cases) and recombinant (4 cases) factor concentrates were given in various infusion sets. Data concerning amount infused (4300 to > 100,000 IU), number of days of exposure to factor concentrates (1 to > 100), and inhibitor characteristics (alloantibodies, 3 LR, 7 HR) were collected. Regarding hemophilia genotype, we found missense mutations in four patients, intron-22 inversions in two, and one small deletion in one; the genotype in three was unknown. In conclusion, only 3 out of 10 patients who developed an inhibitor after CI showed the typical risk profile for inhibitor formation, which is severe hemophilia A with a severe gene defect and less than 50 days of exposure to coagulation factor concentrates. Especially striking was the finding that 50% of the patients who developed inhibitors had mild to moderate hemophilia A. Our data point to the existence of a so-far unknown factor, related to CI, that might lead to inhibitor formation.