Background Parkinson’s disease is a degenerative brain disease related to the accumulation of an abnormally aggregated alpha-synuclein protein. A hypothesis was presumed that this protein will be transported retrogradely from the gastrointestinal tract ultimately leading to the disease. Various epidemiologic studies have shown conflicting results. This study reports the prevalence of appendectomy in Jordanian parkinsonian patients and compares it to controls seen at one major teaching hospital in Jordan. This is a retrospective study of 266 patients compared to a control group of 500 patients randomly selected from the hospital. The prevalence of appendectomy in the 2 groups was studied. Results The rate of appendectomy in patients and controls was 26/266 (9.8%) and 27/500 (5.4%), respectively (relative risk 1.30, odds ratio 1.81, χ2, p = 0.026). Appendectomy in the patients was independent of gender (χ2, p = 0.297). Also, there was no difference in patients with and without appendectomy regarding their age, age at diagnosis of PD, and duration of use of levodopa (p = 0.827, 0.960, and 0.688, respectively, Student t test). The mean duration from appendectomy to the diagnosis of the disease varied widely 23 ± 18.7 years, range −12–59 years. Conclusions Appendectomy occurred significantly more frequent in patients with Parkinson’s disease than in control. There was no difference regarding the age of onset of disease in the patients with and without appendectomy. Though the appendix in this study seems to have a protective role against the development of the disease, the relationship is quite complex requiring prospective in-depth evaluation.