BACKGROUND Acute appendicitis (AA) in an early stage is difficult to distinguish from other (self-limiting) causes of acute abdominal pain (e.g. constipation and gastroenteritis), resulting in missing 19% of children with AA at first presentation in primary care and 70% of non-AA cases among referrals. OBJECTIVE To evaluate the impact of the use of a diagnostic strategy for acute appendicitis (AA), which consists of a clinical prediction rule (cPR) including C-reactive protein point-of-care test (CRP POCT), on referral efficiency in children with acute abdominal pain in primary care, as compared to usual care. STUDY DESIGN This is a cluster randomized controlled trial in primary care with a process evaluation. GPs in the intervention group will use an externally validated cPR based on symptoms and signs selectively followed by a CRP POCT in the medium risk group. GPs from general practices allocated to the control group will provide care and diagnosis as usual, i.e. following recommendations of the Dutch College of GPs guideline 'abdominal pain in children'. STUDY POPULATION Children aged 4 to 18 years presenting to their general practitioner (GP) with acute abdominal pain. OUTCOME MEASURES Primary outcome: referral efficiency (proportion non-referrals in non-AA patients during 30 days follow-up). Secondary outcomes: safety (proportion of referrals in AA patients during the first consultation), proportion of children with CRP-POCT, proportion of children with planned reassessment, child anxiety, parent or child satisfaction, quality of life, and costs.