Ankylosing spondylitis (AS) is very often associated with human leukocyte antigen (HLA), particularly HLA-B*27. However, the strength of this association and clinical features may vary in different ethnic groups. Our study aims to assess the distribution of HLA-A, -B, -Cw and DRB1 alleles in Moroccan patients with AS and to compare the clinical features of AS and the frequencies of HLA-B27 in patients from Morocco with other series. Seventy-five patients diagnosed with AS and assessed for clinical manifestations were selected and compared to 100 healthy controls. HLA class I and II antigens were typed by polymerase chain reaction sequence-specific oligonucleotide. HLA-B27 subtypes were studied by polymerase chain reaction amplification with sequence-specific primers. HLA-B27 was found in 64% of patients. It was positively associated with younger age at disease onset, family history, and uveitis while it had a negative association with late onset. Six B*27 subtypes were identified in the AS group. HLA-B*2705 and B*2702 were the most common observed subtypes. Among other HLA genes, a significant increase in the prevalence of HLA-Cw*02 and HLA-DRB*15 was found in AS patients. HLA-B27 is involved in the predisposition of AS in the Moroccan population. HLA-B*2705 and B*2702 were the predominant subtypes supporting previous reports in Caucasian spondyloarthropathies. Other HLA genes, HLA-Cw*02 and HLA-DRB1*15, seem to confer predisposing effect to the disease. However, the lower frequency of HLA-B27 compared to the literature in our study suggests the existence of different genetic and/or environmental factors in Morocco.