BACKGROUND Nurses run primary health centres in Thailand. We examined whether clinical guidelines improved the quality of the care they provide. METHODS Eighteen nurse-led health centres randomized to (a) guidelines, receiving a training workshop plus educational outreach visit, with guidelines for children (acute respiratory tract infection and diarrhoea) and adults (diazepam prescribing and diabetes management) or (b) usual care. Outcomes were changes at 6 months in antibiotic use, diazepam prescribing, drug costs per patient, and a composite process index for diabetes care. RESULTS Baseline prescribing was high for antibiotics (37% of all attendees), and no difference between intervention and control sites was detected at follow-up for this variable. In children (0-5 years old), antibiotics were widely used for acute respiratory tract infection (34%), and fell with guidelines (intervention: 42% at baseline to 27% at follow-up; control: 27-30%, P = 0.022), with an associated fall in drug costs per patient. Antibiotics were widely prescribed for diarrhoea in children (91%), but no change was detected with guidelines. In adults, diazepam prescribing at baseline was high (17%), and fell in the guidelines group (intervention: 17-10%; control 21-18%; P = 0.029). Diabetes care was generally good, and changed little with guidelines. CONCLUSION Staff at primary health centres over-prescribe antibiotics in children and tranquilizer in adults. Clinical guidelines implemented with workshops and educational outreach visits improved some but not all aspects of prescribing in the short-term.