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Objective NSAIDs are first-line therapy in axial SpA (axSpA). The proportion of patients responding to NSAIDs and differences between AS and non-radiographic axSpA (nr-axSpA) in this regard have not been studied in detail to date. The aim of this study was to examine the proportion of patients with AS and nr-axSpA responding to NSAIDs according to current treatment recommendations. Methods Consecutive anti-TNF-naive patients with nr-axSpA and AS (n = 50 each) were included if their BASDAI score was ⩾4 without having received maximal NSAID doses. In case of a BASDAI score ⩾4 1 week later, another NSAID was prescribed. For the next 3 weeks, continuous intake of maximal doses was recommended but patients could reduce doses in case of intolerance or improvement. MRI of the SI joints was performed at baseline and week 4. Results All outcomes except for CRP and MRI scores improved significantly after 4 weeks of NSAIDs, with no difference between axSpA subgroups. An Assessment of SpondyloArthritis international Society 40% (ASAS40) response and partial remission rates were 35 and 16% at week 4, respectively. At the same time point, a BASDAI score ⩾4 was still present in 44% of patients, 30% of which had reduced NSAID doses, partly due to intolerance (38%). Only 13% of all patients had continuously taken NSAIDs at the maximal dosage, but there was no difference in the efficacy outcome compared with those who had taken reduced doses. Conclusion AS and nr-axSpA patients had similar response rates to NSAIDs while objective signs of inflammation did not change over 4 weeks. Only a minority of patients was willing to take maximal doses of NSAIDs, and ⩾40% patients remained candidates for TNF blockers. These results may influence future trial designs.