AIM:To evaluate the clinical presentation, response to prophylactic therapy and outcome of children with cyclic vomiting syndrome (CVS) in Shiraz, Iran. METHODS:During a period of 11 years (March 1994 to March 2005, 181 consecutive children with a final diagnosis of CVS were evaluated, treated and followed in our center. Patients were randomized to receive either amitriptyline or propranolol as prophylactic treatments. RESULTS:There were 88 boys and 93 girls with mean age of onset of symptoms of 4.9 ± 3.3 years (range, neonatal period to 14 years), the mean age at final diagnosis was 6.9 years (range, 1.5 to 14), and the mean duration between the onset of the first attack and the final diagnosis of CVS was 2 ± 1.81 years (range, 1/6 to 8). The mean duration of each attack was 4.26 days (range, from few hours to 10 d) and the mean interval between the attacks was 1.8 mo (range, 1 wk to 12 mo). The time of onset of the attacks was midnight to early morning in about 70% of cases. Amitriptyline was effective in 46 out of 81 (56%) patients (P < 0.001). Propranolol appeared to have a superior action and was effective in 74 out of 83 (92%) patients (P < 0.0001). CONCLUSION:There is a significant lag time between the onset of clinical symptoms and the final diagnosis of CVS in our area. In patients with typical clinical presentations www.wjgnet.com of CVS, who are examined by an experienced physician, invasive workup is not necessary. Propranolol appears more effective than amitriptyline for prophylactic use in children with CVS.