This study was conducted to determine differences in ankylosing spondylitis (AS) between men and women in terms of clinical characteristics, biological features, structural severity and quality of life (QoL). A total of 130 consecutive AS patients fulfilling the modified New York criteria were included. Sociodemographic data were collected. The activity of disease was assessed by the Bath ankylosing spondylitis disease activity index (BASDAI) and the functional disability by the Bath Ankylosing spondylitis functional index (BASFI). Spinal mobility was measured using the occiput-to-wall distance, chest expansion, Schober index and the Bath Ankylosing Spondylitis Metrology Index (BASMI). The Bath Ankylosing Spondylitis Radiologic Index (BASRI) was used to evaluate structural damage. Fatigue was evaluated using a visual analogue scale and the QoL was measured by using the generic instrument SF-36. Laboratory tests included the erythrocyte sedimentation rate (ESR) and the C-reactive protein (CRP). In our sample, there were 87 (66.9%) men and 43 (33.1%) women. Women had significantly lower educational levels but there were no differences in socioeconomic status, age at onset, diagnosis delay, disease duration or treatments. Also, women had higher clinical disease activity (morning stiffness and BASDAI score), higher number of tender joints, more severe enthesitis and higher scores of fatigue (for all p ≤ 0.05). Moreover, hip involvement was more prevalent in men and the impairment of spinal mobility was significantly worse compared to women (for all p ≤ 0.001). Men had worse radiographic damage and lower scores in physical and social domains of QoL, but there were no differences in functional impairment scores. In this study, we noticed that AS presents differently according to gender in our patients. More longitudinal studies seem to be necessary to identify gender-related parameters of disease, thing that may help in diagnosis and therapeutic management of our AS patients.