Introduction Tibial osteotomy by the hemicallotasis technique is a clean elective operation. With external fixation pins inserted, close to the knee joint, the infection prophylaxis should be considered. The primary aim was to investigate the differences in the postoperative use of antibiotics during the time in external fixation between administrating prophylactic antibiotics for 3 days or as a single dose in patients operated on by the hemicallotasis technique for knee deformities. Secondary aims were to study the differences in pin-site infection rate and grade and complications. Material and methods A total of 106 consecutive patients of mean age 52 years (range 18-69) operated on by the hemicallotasis technique for knee deformities were included in this prospective study. Sixty patients were prescribed prophylactic antibiotics for 3 days and 46 patients as a single dose. Chlorhexidine (5 mg/ml) in alcohol (70% ethanol) was used as cleansing agent in the pin-site care. The power of the study was calculated to 80% to detect a difference in the postoperative use of antibiotics for 7 days during the treatment in external fixation. Results There were no differences in postoperative use of antibiotics between 3 days administration or a single dose of prophylactic antibiotics. This was the case with infection rate and grade, positive bacterial cultures, presence of Staphylococcus aureus, nor positive culturing from the tip of the pins at removal. Neither were there any differences in numbers of loose pins and complications. Conclusion There were no differences between 3 days of administration of prophylactic antibiotics and one single dose. One single dose of prophylactic antibiotics is appropriate together with a pin-site concept preventing pin-site infection in patients operated on by hemicallotasis osteotomy.