Background: Off-label use, the practice of prescribing pharmaceu­ticals outside a drug’s approved label, is very common in paediatrics. Health agencies, including the WHO, need to analyse this phenomenon in order to discuss appropriateness of use, and define common criteria for guidelines of off-label drug use in children. A comparison of drug labels with scientific evidence and with current use may help in more systematic understanding of these issues. Objectives: To investigate off-label use by comparing prescribing data, drugs labels and evidence using a case study of antiemetic drugs for gastroenteritis in children. Methods: We present data on seven antiemetics currently used. Drugs use were drawn from the Italian Seven Hospitals Prescribing Survey in Paediatric Emergency Departments, which involved 904,531 children over four years (2004–2007). Cochrane reviews were used as reference evidence, other systematic reviews and RCTs served to update on new studies. Results: Antiemetics were largely prescribed, although there were wide differences across the seven units (range 0.1% to 5.3% of total prescribed drugs). An early analysis suggests a high level of inconsistency between use in clinical practice, evidence and drug labels (Table 1). Domperidon is registered for acute vomiting from any cause and was the most used drug, despite very low supporting evidence on effectiveness in gastroenteritis. Ondansetron is registered only for chemotherapy and post-operative vomiting though several RCTs have proven its efficacy in acute gastroenteritis. Conclusions: Off-label prescribing is a widespread problem. Cochrane reviews may help in delineating patterns of inappropriate prescribing, but also areas where off-label use may be appropriate. The process of labelling needs to better harmonised with scientific evidence, including Cochrane reviews.