Introduction: In clinical settings, acute anterior uveitis (AAU) could be the first presentation of ankylosing spondylitis (AS). Based on this hypothesis, we investigate whether AAU is a risk factor in developing AS later by using National Health Insurance Research Database (NHIRD) in Taiwan. Materials and Methods: This cohort comparison study used longitudinal Taiwanese NHIRD to probe the relative risk odds of AAU for AS development, and consisted of all patients diagnosed with AAU (n = 5621) (ICD-9-CM codes 364.00). The relative risks of AS between AAU patients and controls were compared by estimating the crude hazard ratio with logistic regression. Kaplan–Meier analysis was used to calculate the cumulative incidence rates of developing AS, and a log-rank test was used to analyze the differences between the survival curves. Separate Cox proportional hazard regressions were performed to compute the AS-free rate after adjusting for possible confounding factors such as age and sex. Results: The crude hazard ratio was 2.667 for the AAU group, and the adjusted hazard ratio was 2.705 for the AAU group. The observation time of the AS-free group was shorter for AAU patients compared with the control group (1507 versus 1578 days). Moreover, in the AAU patients, the younger age onset of AAU (less than 30 years old here) would lead to an earlier diagnosis of AS later with a median of 1445.5 (742–2241) versus 1544 (819–2289) days of survival for the group of age onset of AAU greater than 30 years old. The difference is statistically significant (p < 0.05). Conclusions: AAU was a risk factor for AS. To identify AAU as an extra-articular manifestation is crucial for early diagnosis and treatment of AS and containing functional loss accordingly. Full article