The aim of the study was to compare the spondyloarthropathy of ankylosing spondylitis (AS) to that of psoriatic arthritis (PsA). Forty patients with AS and 66 patients with PsA underwent a complete assessment according to a standard protocol, including radiographic evaluation and HLA typing. A logistic regression analysis was performed controlling for age, arthritis duration, and sex. A higher frequency of inflammatory neck and back pain and stiffness (p < 0.0002), limitation of back movements (p < 0.0006), grade 4 sacroiliitis (p = 0.007), and syndesmophytes (p = 0.005) was noted in AS, while peripheral arthritis was more common and more severe in patients with PsA (p = 0.002). A lower frequency of HLA B17 (p = 0.02), and a higher frequency of HLA B27 (p = 0.0001), and Cw2 (p < 0.01) was found in AS compared to PsA. Thus, there are clinical, radiologic, and genetic differences in disease expression of the SA of AS and PsA, supporting their classification as distinct entities.