Abstract: Background: Serious lower respiratory tract infections (SLRTIs), especially Streptococcus pneumoniae (SP)-related pneumonia cause considerable morbidity and mortality. Chest imaging, sputum and blood culture are not routinely obtained by general practitioners (GPs). Antibiotic therapy is usually started empirically. The BinaxNOW (R) and Urine Antigen Detection (UAD) assays have been developed respectively to detect a common antigen from all pneumococcal strains and the 13 pneumococcal serotypes present in the vaccine Prevenar 13 (R) (PCV13). Methods: OPUS-B was a multicentre, prospective, case-control, observational study of patients with SLRTI in primary care in Belgium, conducted during two winter seasons (2011-2013). A urine sample was collected at baseline for the urine assays. GPs were blinded to the results. All patients with a positive BinaxNOW (R) test and twice as much randomly selected BinaxNOW (R) negative patients were followed up. Recorded data included: socio-demographics, medical history, vaccination history, clinical symptoms, CRB-65 score, treatments, hospitalization, blood cultures, healthcare use, EQ-5D score. The objectives were to evaluate the percentage of SP SLRTI within the total number of SLRTIs, to assess the percentage of SP serotypes and to compare the burden of disease between pneumococcal and non-pneumococcal SLRTIs. Results: There were 26 patients with a BinaxNOW (R) positive test and 518 patients with a BinaxNOW (R) negative test. The proportion of pneumococcal SLRTI was 4.8 % (95 % CI: 3.1 %-7.2 %). Sixty-eight percent of positive cases showed serotypes represented in PCV13. In the BinaxNOW-positive patients, women were more numerous, there was less exposure to young children, seasonal influenza vaccination was less frequent, COPD was more frequent, the body temperature and the number of breaths per minute were higher, the systolic blood pressure was lower, the frequency of sputum, infiltrate, chest pain, muscle ache, confusion/disorientation, diarrhoea, pneumonia and ...