Aim. To evaluate the efficacy and safety of intravenous methylprednisolone (MP) 500 mg in patients with active ankylosing spondylitis (AS) and the inefficiency, intolerability of or contraindications to treatment with 2 or more non-steroidal anti-inflammatory drugs (NSAIDs). Subjects and methods. The investigation enrolled 20 patients (age, 35.35±8.19 years) with a 10.2±9.2year history of AS who met the modified New York criteria) and had its activity defined as the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥4 scores and an inadequate response to and intolerance of ≥2 NSAIDs; there were 13 (65%) men. MP was given in a single intravenous dose of 500 mg. The main efficiency criterion (primary study endpoint) was considered to be the number of patients who had achieved an ASAS20 response at week 2. Additional rating criteria (secondary endpoints) (improved BASDAI/ASDAS; decreased erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels; the number of patients achieving ASAS20/40/5/6 responses and ASAS partial remission, and improved ASDAS) were calculated 2, 4, and 12 weeks after MP administration. Safety was monitored estimating the frequency of adverse events (AEs) and controlling vital functions and laboratory indicators. Results. Nine (45%) patients achieved an ASAS40 response at week 2. ASDAS was 3.48 at baseline and 2.21 at week 2 (p<0.0001). ASDAS clinical improvement was established in 11 (55%) patients at week 2. There were decreases in BASDAI from 6.6 to 3.7 at week 2, to 3.5 at week 4, and to 3.2 at week 12 (p<0.001). CRP levels declined from 6.1 to 3.15 mg/l at week 2 (p<0.05), to 2.85 mg/l at week 4 (p<0.001), and to 4.6 mg/l at week 12 (p<0.05). ESR was 6.5 mm/h at baseline, 5.5 mm/h at week 2 (p<0.05), 6.0 mm/h at week 4, and 7.0 mm/h at week 12 (p > 0.05). A total of 13 AEs were recorded and no serious AEs were noted. Conclusion. Pulse therapy with MP 500 mg is safe and effective in the short-term treatment of patients with active AS who have achieved no benefits of NSAIDs.