Background The occurrence of preterm birth remains a complex public health condition. It is considered the main cause of neonatal morbidity and mortality, resulting in a high likelihood of sequelae in surviving children. With variable incidence in several countries, it has grown markedly in the last decades. In Brazil, however, there are still difficulties to estimate its real occurrence. Therefore, it is essential to establish the prevalence and causes of this condition in order to propose prevention actions. This study intend to collect information from hospitals nationwide on the prevalence of preterm births, their associated socioeconomic and environmental factors, diagnostic and treatment methods resulting from causes such as spontaneous preterm labor, prelabor rupture of membranes, and therapeutic preterm birth, as well as neonatal results. Methods/Design This proposal is a multicenter cross-sectional study plus a nested case-control study, to be implemented in 27 reference obstetric centers in several regions of Brazil (North: 1; Northeast: 10; Central-west: 1; Southeast: 13; South: 2). For the cross sectional component, the participating centers should perform, during a period of six months, a prospective surveillance of all patients hospitalized to give birth, in order to identify preterm birth cases and their main causes. In the first three months of the study, an analysis of the factors associated with preterm birth will also be carried out, comparing women who have preterm birth with those who deliver at term. For the prevalence study, 37,000 births will be evaluated (at term and preterm), corresponding to approximately half the deliveries of all participating centers in 12 months. For the case-control study component, the estimated sample size is 1,055 women in each group (cases and controls). The total number of preterm births estimated to be followed in both components of the study is around 3,600. Data will be collected through a questionnaire all patients will answer after delivery. The data will then be encoded in an electronic form and sent online by internet to a central database. The data analysis will be carried out by subgroups according to gestational age at preterm birth, its probable causes, therapeutic management, and neonatal outcomes. Then, the respective rates, ratios and relative risks will be estimated for the possible predictors. Discussion These findings will provide information on preterm births in Brazil and their main social and biological risk factors, supporting health policies and the implementation of clinical trials on preterm birth prevention and treatment strategies, a condition with many physical and emotional consequences to children and their families.