Background: Appendicitis is one of the most common causes of acute abdominal surgeries. The importance of parasitic etiologies in the pathogenesis of appendicitis is not well known in appendectomy specimens on a large scale in southwestern Iran. The current study aimed to retrospectively assess the demographic data and histopathological records of appendicitis in a 28-year period in Fars province, southwestern Iran. Materials and Methods: Histopathological records of 13,013 patients who had undergone surgeries for appendicitis at Dr. Ali Shariati Hospital, affiliated with the Fasa University of Medical Sciences from December 1993 to January 2021 were reviewed and data concerning the patients' demographic data and histopathological records were retrieved from each record. More than 6800 archived microscopic glass slides were also reviewed. Results: From a total of 13,013 histopathological records of surgical excisions of appendicitis that were reviewed over a 28-year period, 8,189 (62.9%) were male and 4,842 (37.1%) were female. Patients' age ranged from 2 to 98 years, with a mean age of 24.68±19.87 years. The most common inflammatory changes were 5,687 (43.7%), 1,228 (9.4%), 670 (5.1%), 522 (4%), and 363 (2.8%) cases of acute appendicitis, suppurative appendicitis, early acute appendicitis, gangrenous appendicitis, and perforated appendicitis respectively. Microscopically, no viral inclusions, fungal elements, and histopathologic findings of bacterial causes were found. Parasitic infections such as helminthiasis were detected in 74 (0.6%) cases aged from 6 to 63. Enterobiasis (Syn. oxyuriasis, pinworm infection) accounted for 73 (98.6%) of the 74 helminthiases, while ascariasis accounted for 1 (1.4%). Out of 74 cases, 29 (39.2%) showed evidence of appendicitis. Conclusion: The results suggest that although parasitic agents are minor causes of appendicitis, these agents should be kept in mind during differential diagnosis. However, whether every parasitic infection leads to appendicitis is controversial.