Background: Appendicitis is a frequent reason for hospital admissions. Elevated C-reactive protein, white blood cell count, and serum bilirubin have been suggested as individual markers for appendicitis and appendiceal perforation. The aim of this study was to analyze if a combination of serologic markers could increase the prognostic accuracy of diagnosing non-perforated and perforated appendicitis. Material and Methods: Demographic data, histological findings, blood tests, and clinical symptoms were collected on all patients who underwent a diagnostic laparoscopy, a laparoscopic appendectomy, or conventional (open) appendectomy between May 2009 and May 2012 from a surgical department. The patients were grouped into those with either perforated appendicitis, non-perforated appendicitis, or differential diagnosis. Univariate and multivariate models were used to identify which markers were useful in predicting acute and perforated appendicitis, and receiving operating characteristics curves were used to find the specificity, sensitivity, and the negative and positive predictive values. Results: A total of 1008 patients were operated under suspicion of appendicitis. From these, 700 patients had a pathologically verified inflamed appendix and 190 had a perforated appendix. Patients with acute appendicitis had significantly higher blood levels of white blood cell, bilirubin, C-reactive protein, and alanine transaminase than patients without appendicitis. Patients with perforated appendicitis had significantly higher levels of white blood cell, bilirubin, and C-reactive protein than patients with nonperforated appendicitis. The highest positive predictive value to discriminate between acute appendicitis and non-appendicitis was of a linear regression model combining white blood cell count, bilirubin, and alanine transaminase. C-reactive protein levels and a linear regression model, including white blood cell count, bilirubin, and C-reactive protein levels as variables, had the highest negative predictive values when discriminating between perforated and non-perforated appendicitis. Conclusion: Combining blood markers was useful in predicting appendicitis and perforated appendicitis. In addition to C-reactive protein and white cell count, blood levels of bilirubin, and alanine transaminase may be useful.