Nine patients with sickle cell disease (SCD) were operated upon at our hospital for acute appendicitis, comprising only 0.43% of the total appendicectomies performed at our institution. Three appendices were acutely inflamed and six (66.7%) were perforated. Histologic evaluation of the six perforated specimens revealed congestion and haemorrhage by sickled erythrocytes (RBCs) in addition to acute transmural inflammatory cell infiltrates. The mucosa was extensively ulcerated, with haemorrhage both within the lumen and in the appendiceal wall. The blood vessels were dilated and packed with sickled RBCs. Two of the three acutely inflamed appendices showed features of acute transmural appendicitis, with marked congestion and haemorrhage by sickled RBCs. The third did not show any acute inflammatory cell infiltrate, however, the mucosa was partly ulcerated with both mucosal and intraluminal haemorrhage. These findings suggest that acute appendicitis is different in patients with SCD: while it is not common, when it does develop it has a rapid course with a high incidence of perforation due to blockage of appendiceal vessels by sickled RBCs, leading to transmural necrosis.