Objective Familial Mediterranean Fever (FMF) is an autoinflammatory disease that is commonly present with recurrent episodes of fever, peritonitis, pleuritis or arthritis. Enthesitis and sacroilitis can also be seen in FMF. Spondylitis is a less common manifestation of joint involvement in FMF and there are controversial publications about whether this involvement is FMF-related or coincidentally. The aim of this study was to provide a comparison between ankylosing spondylitis (AS) patients and FMF patients with AS. Methods A total of 404 patients who 360 of them was AS and 44 was FMF patients with AS (in accordance with Tel Hashomer) patients with AS (in accordance with modified New York criteria) were included in this study. All cases were evaluated retrospectively and patient's demographic and clinical data were recorded. Results The mean age was 34.5 +/- 8.6 years and 61.4% of patients were female in FMF group. In AS group, the mean age was 41.2 +/- 10.8 years and 67.8% of patients were male. In AS group, 92% of patients had inflammatory back pain, 51% had hip pain, 30% had heel pain, 14% had peripheral arthritis and 11% had uveitis. In FMF group, 98% of patients had inflammatory back pain, 59% had hip pain, 48% had heel pain, 43% had peripheral arthritis and 4.5% had uveitis. Syndesmophyte and enthesitis on X-ray were seen in 18% and 22% of AS patients, and 7% and 41% of FMF patients with AS, respectively. There were significant differences between AS patients and FMF patients with AS in terms of heel pain (P: .017), peripheral arthritis (P: .000) and enthesitis (P: .006). Conclusion Peripheral arthritis and enthesitis were more frequent, and uveitis and syndesmophyte were less frequent in FMF patients with spondylitis than AS patients. When we look at gender differences, clinical and genetic features, it seems to be different condition from AS.