Nissen fundoplication is a generally accepted treatment for severe gastro-oesophageal reflux after conservative management has failed. The surgical techniques and the complications that may develop following the operation have been well described. However, necrosis of the spleen is a rare complication. We report here a patient with Down syndrome with a vanishing spleen after a Nissen fundoplication, who died of overwhelming pneumococcal septic shock 7 months after the operation. Vascular anomaly in Down syndrome, inadvertent ligation of the splenic artery or volvulus of the spleen may have caused a compromised splenic arterial circulation.Conclusion Nissen fundoplication may be associated with vanishing spleen and, consequently, with devastating consequences.