Evidence before this study We searched PubMed on June 30, 2016, for English-language cohort studies published since Jan 1, 1980, of patients with invasive listeriosis worldwide with the keywords " listeria " , " listeriosis " , " maternal " , and " neurolisteriosis ". Studies had to include epidemiological or clinical data on listeriosis. All clinical forms of infection were included (bacteraemia, neurolisteriosis, and maternal–neonatal infection). Host risk factors for listeriosis have been well identified, but the clinical features and prognostic factors of the disease are based on retrospective studies compiling heterogeneous data or random collected cases. Furthermore, no clinical trial has ever been done and medical management is not evidence based. Added value of the study Our study is the first prospective clinical study focusing on all forms of invasive listeriosis. The study is based on a national mandatory system that allowed the nearly complete capture of microbiologically proven cases. The study shows a higher burden of listeriosis than reported before: more than 80% of infected mothers experienced major fetal or neonatal complications (fetal loss, very high prematurity, early or late onset disease); only 39% of patients with neurolisteriosis survived and fully recovered. The study provides important new data to improve management and predict outcome in listeriosis, such as determination of the time window for fetal losses (<29 weeks of gestation and <3 days of adequate management) and new factors independently associated with mortality. Our data show the deleterious effect of adjunctive dexamethasone in neurolisteriosis, and argue for the use of beta-lactam and gentamicin or co-trimoxazole over other antimicrobials for bacteraemia and neurolisteriosis. Implications of all the available evidence Given the practical difficulties in completing clinical trials in listeriosis, these results could guide clinical practice and suggest that combined amoxicillin and gentamicin should be considered the first-line combination in invasive listeriosis, and that adjunctive dexamethasone should be avoided in cases of confirmed listeriosis. ABSTRACT Background: Listeriosis is a severe foodborne infection and a notifiable disease in France. We did a nationwide prospective study to characterise its clinical features and prognostic factors.