Inflammation at the entheses is a distinguishing feature of spondyloarthritis (SpA). Enthesitis at the heel is the most common location and is often chronic, refractory to standard treatment and may have socioeconomic consequences. The objective of this study was to investigate the efficacy of etanercept in refractory heel enthesitis related to SpA.The present work was a 12-week, randomised, double-blind, placebo-controlled study compared etanercept with placebo in patients with SpA according to Amor's criteria, and heel enthesitis proven by MRI. The primary efficacy end point was the normalised net incremental area under the curve (AUC) between randomisation and week 12 for the patient's global assessment (PGA) of disease activity. Secondary end points included change from baseline in PGA, heel pain, the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC) function subscale and improvement in enthesitis as measured by MRI.A total of 24 patients were randomised. Mean normalised net incremental AUC for PGA of disease activity over 12 weeks was significantly greater in the etanercept versus placebo group: -28.5 versus -11.1, respectively (p=0.029). Significant improvements were also reported in the etanercept versus placebo group for PGA, -37.6 versus -11.6 (p=0.007); heel pain, -36.7 versus -13.1 (p=0.022); and WOMAC function, -23.2 versus -7.8 (p=0.024). No significant changes were observed in the MRI findings between groups. No unexpected adverse events or changes in laboratory values or vital signs.This trial is the first randomised placebo-controlled study of an anti-tumour necrosis factor (TNF) agent in refractory heel enthesitis in patients with SpA. It demonstrates that etanercept has a statistically significant and clinically relevant benefit in such patients. ClinicalTrials.gov identifier NCT00420303.