Monocytes of patients with ankylosing spondylitis (AS) have toll-like receptor 4 (TLR4) overexpression on their monocytes. Myeloid-related protein (MRP) 8/14 protein complexes are calcium-binding proteins, which act as endogenous ligands to TLR4. Thus, we studied the levels of MRP8/14 in adult AS patients. MRP8/14 levels were assessed in 99 adult AS patients satisfying Assessments in Ankylosing Spondylitis International Society 2010 criteria and 71 healthy controls by ELISA. Patient disease parameters like patient and physician global assessment, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), swollen and tender joint count, entheseal count by Maastricht enthesitis index, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were also recorded. Levels were reassessed in 23 patients after 2-5 months of treatment with NSAIDs. All values are in median (IQR). The serum MRP8/14 levels in patients [34.1 (17.94-264.58) mu g/ml] were significantly higher than in healthy controls [4.94 (IQR 3.01-8.32) mu g/ml (p < 0.0001)]. Patients with peripheral arthritis (n = 50) had higher levels than those with pure axial disease (n = 49) [40.63 (IQR 28.41-73.15) mu g/ml vs. 23.72 (11.04-61.55) mu g/ml; p = 0.012]. Levels of MRP8/14 correlated with AS Disease Activity Score (DAS)-CRP (r = 0.23, 95%CI = 0.038-0.422, p = 0.02) and CRP (r = 0.28, 95%CI = 0.081-0.45, p = 0.01), and the correlation was better in early disease [<= 5 years disease duration; r = 0.40, p = 0.007 and r = 0.57, p = < 0.0001, respectively]. Baseline levels were higher in treatment responders than in non-responders [51.17 vs. 32.22 mu g/ml; p = 0.02]. Change in MRP8/14 levels correlated with change in BASDAI and ASDAS-CRP (r = 0.489, p = 0.018 and r = 0.498, p = 0.016, respectively). MRP8/14 levels may be used as a biomarker for activity, peripheral arthritis, and response to therapy.