Objective: To assess the medicalising effect of prescribing antibiotics for sore throat. Setting: 11 general practices in England. Design: Randomised trial of three approaches to sore throat: a 10 day prescription of antibiotics, no antibiotics, or a delayed prescription if the sore throat had not started to settle after three days. Patients: 716 patients aged 4 and over with sore throat and an abnormal physical sign: 84% had tonsillitis or pharyngitis. Outcome measures: Number and rate of patients making a first return with sore throat, pharyngitis, or tonsillitis. Early returns (within two weeks) and complications (otitis media, sinusitis, quinsy). Outcomes were documented in 675 subjects (94%). Results: Mean follow up time was similar (antibiotic group 1.07 years, other two groups 1.03 years). More of those initially prescribed antibiotics initially returned to the surgery with sore throat (38% v 27%, adjusted hazard ratio for return 1.39, 95% confidence interval 1.03 to 1.89). Antibiotics prescribed for sore throat during the previous year had an additional effect (hazard ratio 1.69, 1.20 to 2.37). Longer duration of illness (> 5 days) was associated with increased return within six weeks (hazard ratio 2.90, 1.70 to 4.92). Prior attendance with upper respiratory conditions was also associated with increased reattendance. There was no difference between groups in early return (13/238 (5.5%) v 27/437 (6%)), or complications (2/236 (0.8%) v3/434 (0.7%)). Conclusions: Complications and early return resulting from no or delayed prescribing of antibiotics for sore throat are rare. Both current and previous prescribing for sore throat increase reattendance. To avoid medicalising a self limiting illness doctors should avoid antibiotics or offer a delayed prescription for most patients with sore throat. Sore throat is one of the commonest presentations of upper respiratory illness in primary care and attendence is increasing Complications are rare with no, or delayed, antibiotic prescription Prescribing antibiotics increases reattendance for future episodes Unless patients are very ill general practitioners should consider exploring concerns, explain the natural history, and avoid or delay prescribing antibiotics