Objectives To analyse the long-term relationship between disease activity and radiographic damage in the spine in patients with ankylosing spondylitis (AS). Methods Patients from the Outcome in AS International Study (OASIS) were followed up for 12 years, with 2-yearly clinical and radiographic assessments. Two readers independently scored the X-rays according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Disease activity measures include the Bath AS Disease Activity Index (BASDAI), AS Disease Activity Index (ASDAS)-C-reactive protein (CRP), CRP, erythrocyte sedimentation rate (ESR), patient's global assessment and spinal pain. The relationship between disease activity measures and radiographic damage was investigated using longitudinal, autoregressive models with 2-year time lags. Results 184 patients were included (70% males, 83% HLA-B27 positive, mean (SD) age 43 (12) years, 20 (12) years symptom duration). Disease activity measures were significantly longitudinally associated with radiographic progression. Neither medication nor the presence of extra-articular manifestations confounded this relationship. The models with ASDAS as disease activity measure fitted the data better than models with BASDAI, CRP or BASDAI+CRP. An increase of one ASDAS unit led to an increase of 0.72 mSASSS units/2 years. A 'very high disease activity state' (ie, ASDAS >3.5) compared with 'inactive disease' (ie, ASDAS = 18 years symptom duration (0.84 vs 0.16 mSASSS units per ASDAS unit). Conclusions This is the first study showing that disease activity contributes longitudinally to radiographic progression in the spine in AS. This effect is more pronounced in men and in the earlier phases of the disease.