Objective: The purpose of this clinical trial was to evaluate the impact of a 4-month comprehensive protocol of strengthening and flexibility exercises developed by our research group versus conventional exercises for patients with Ankylosing Spondylitis (AS) on functional and mobility outcomes., Design: Randomized controlled trial. Forty-five patients diagnosed with AS according to the modified criteria of New York were allocated to control or experimental groups using a random numbers table. The control group was treated with a conventional protocol of physical therapy in AS, whereas the experimental group was treated with the protocol suggested by our research group. The conventional intervention consisted of 20 exercises: motion and flexibility exercises of the cervical, thoracic, and lumbar spine; stretching of the shortened muscles; and chest expansion exercises. The experimental protocol is based on the postural affectation of the AS and the treatment of the shortened muscle chains in these patients according to the Global Posture Reeducation (GPR) method. This intervention employs specific strengthening and flexibility exercises in which the shortened muscle chains are stretched and strengthened. The study lasted 4 mos. During this period, patients received a weekly group session managed by an experienced physiotherapist. Each session lasted an hour, and there were 15 total sessions. Changes in activity, mobility, and functional capacity were evaluated by an assessor blinded to the intervention, using the following previously validated scores from the Bath group: BASMI (tragus to wall distance, modified Schober test, cervical rotation, lumbar side flexion, and intermalleolar distance), BASDAI (The Bath Ankylosing Spondylitis Disease Activity Index), and BASFI (The Bath Ankylosing Spondylitis Functional Index)., Results: Both groups showed an improvement (prepost scores) in all the outcome measures, mobility measures of the BASMI index, as well as in BASFI and BASDAI indexes. In the control group, the improvement in tragus to wall distance (P=0.009) and in lumbar side flexion (P=0.02) was statistically significant. Although the rest of the outcomes also improved, they did not reach a significant level (P>0.05). In the experimental group, the improvement in all the clinical measures of the BASMI index (P<0.01) and in the BASFI index (P=0.003) was statistically significant. The intergroup comparison between the improvement (prepost scores) in both groups showed that the experimental group obtained a greater improvement than the control group in all the clinical measures of the BASMI index, except in tragus to wall distance, as well as in the BASFI index., Conclusions: The experimental protocol developed by our research group, based on the GPR method and specific strengthening and flexibility exercises of the muscle chains, offers promising results in the management of patients suffering from AS. Further trials on this topic are required.