Background and Aims: Delayed or wrong diagnosis in patients with appendicitis can result in perforation and consequently increased morbidity and mortality. Serum bilirubin may be a useful marker for appendiceal perforation. The purpose of this systematic review was to evaluate studies investigating elevated serum bilirubin as a predictor for appendiceal perforation. Material and Methods: Medline, Embase, and Cochrane databases were searched for studies evaluating elevated bilirubin in the diagnosis of perforated appendicitis. Study selection criteria included English language papers evaluating serum bilirubin as a marker of appendiceal perforation in humans. A total of 189 abstracts were screened for eligibility, of which five clinical studies were included in this study. Results: Bilirubin was significantly higher in patients with appendiceal perforation compared with patients with appendicitis without perforation. Elevated serum bilirubin had a sensitivity ranging from 0.38 to 0.77 and a specificity ranging from 0.70 to 0.87 in predicting appendiceal perforation. Conclusions: Elevated serum bilirubin for determining the risk of perforation in appendicitis has low sensitivity but higher specificity. This measure can therefore be used as a supplement in the diagnostic process.