Objective To investigate whether individualised treatment by homeopaths is effective in preventing childhood upper respiratory tract infection (URTI). Methods Open, pragmatic, randomised parallel-group trial with waiting-list group as control. One hundred and sixty-nine children below the age of 10 years, recruited by post from children previously diagnosed with URTI, were randomly assigned to receive either pragmatic homeopathic care from one of five homeopaths for 12 weeks or to a waiting-list control using self-selected, conventional health care. Result There was a significant difference in median total symptom score in favour of homeopathic care (24 points) compared to the control group (44 points) (p = 0.026). The difference in the median number of days with URTI symptoms was statistically significant with 8 days in the homeopathic group and 13 days in the control group (p = 0.006). There was no statistical difference in the use of conventional medication or care between the two groups. Conclusion In this study, there was a clinically relevant effect of individualised homeopathic care in the prevention of URTI in children.