Currently available therapies for the treatment of Ankylosing Spondylitis (AS) target primarily the signs and symptoms of the disease; scant data exist demonstrating an impact on structural progression even for disease-modifying antirheumatic drugs (DMARDs). The European League against Rheumatism (EULAR) and the Assessments in Ankylosing Spondylitis International Society (ASAS) recommend the use of nonsteroidal anti-inflammatory drugs (NSAIDs) as first-line therapy, and these are often used in combination with other agents as patients progress in their treatment. For those patients who do not respond or who have an inadequate response to NSAIDs, TNF-alpha (TNF-α) inhibitors are recommended. The use of conventional DMARDs (e.g., sulfasalazine) is only recommended for patients with peripheral involvement. This report uses longitudinal patient-level claims data to understand the extent to which U.S. physicians adhere to the treatment guidelines set out by ASAS and EULAR by analyzing the use of key therapies. Both newly diagnosed and recently treated AS patient cohorts are examined. Among the newly diagnosed patients, we provide a quantitative analysis of treatment patterns and share by line of therapy, as well as progression between lines, duration of treatment on each line, and use of combination therapy. Among recently treated patients, we quantify a drug’s source of business compared with its competitors, and detail which drugs precede others through an analysis of add-versus-switch patterns. Additional analyses explore persistency and compliance by brand.