Knowledge of the genetic background of patients with inflammatory arthritis may be useful for disease management. The main markers are the HLA-DR-associated Shared Epitope (SE) for Rheumatoid Arthritis (RA) and HLA-B27 for ankylosing spondylitis. We have developed a simple molecular biology-based test to provide this essential information. HLA targets are amplified by polymerase chain reaction (PCR), then simultaneously analyzed using 16 individual hybridization reactions in two 8-well ELISA strips with colorimetric detection. Concordance was evaluated using a cohort of RA patients with known genotype. Using this new assay, 100% concordance was observed with conventional genotyping in RA patients both for HLA-DR SE and B27 genotypes. Seventy-three percent of the patients with destructive RA had at least one susceptible allele within SE, compared to 38% of those patients with non-destructive disease. This new assay, which requires minute amount of blood, could be used to determine the genetic background of inflammatory arthritis, particularly in non-specialized settings and for large-scale clinical trials.