<p><b>OBJECTIVE</b>To investigate the clinical effect and safety of somatostatin in the treatment of postoperative gastrointestinal bleeding in neonates.</p><p><b>METHODS</b>A prospective randomized study was performed, and 126 neonates who underwent surgery for congenital gastrointestinal anomalies were randomly divided into control group, treatment group A, and treatment group B. The neonates in the control group were given routine postoperative hemostasis, and those in the treatment groups were given somatostatin in addition to the treatment for the control group. The neonates in treatment group A were given intravenous injection of somatostatin 0.25 mg as the initial dose and 0.25 mg/h for maintenance, and those in treatment group B were given continuous intravenous pumping of somatostatin at a dose of 3.5 μg/(kg·h). The clinical outcome and complications were compared between the three groups.</p><p><b>RESULTS</b>Compared with the control group, the treatment groups had significantly shortened clearance time in occult blood test for gastrointestinal decompression drainage and a significantly lower degree of the reduction in 24-hour hemoglobin (P<0.05), while there were no significant differences between treatment groups A and B. Compared with the control group, treatment group A had significant reductions in heart rate (HR), respiratory rate (RR), blood pressure (BP), and SaO2 after one hour of treatment (P<0.05 ), but there were no significant differences at the other time points between the two groups (P>0.05). There were no significant differences in monitoring indices between the control group and treatment group B (P>0.05). No neonates in the control group experienced hypoglycemia reaction, and treatment group A had a significantly higher incidence rate of hypoglycemia (20%) than treatment group B (P<0.05).</p><p><b>CONCLUSIONS</b>Somatostatin has a marked clinical effect and good safety in the treatment of neonates with postoperative gastrointestinal bleeding, and the administration of somatostatin by continuous intravenous pumping leads to fewer side effects.</p>