Abstract Objective To describe the methodological aspects of a Prospective Cohort Study of adult oral health in Piracicaba, Brazil. Results This Prospective Cohort Study evaluated adults (20–64 years old) between the years of 2011 and 2015, in Piracicaba, São Paulo, Brazil. The main objective was to evaluate the risk factors for tooth loss in adults. Data were collected at households and selected via probabilistic sampling, through clinical examination of caries, considering as variables the decayed, missing and filled permanent teeth index, need for caries treatment, periodontal disease (Community Periodontal Index and Periodontal Attachment Loss), use and need for dental prosthesis, and presence of visible biofilm. A questionnaire about demographic, socioeconomic and health habits, use of dental services, self-perceived quality of life (Oral Health Impact Profile-14) and health literacy (14-item Health Literacy Scale) was also employed. In 2011, 248 adults participated, and in 2015, 143 (follow-up rate = 57.7%). Despite the follow-up sample loss, most sociodemographic characteristics remained in the participant sample: for example, women (72.0%) (p = 0.534), family income between R$545,00 and R$1090,00 (63.9%) (p = 0.920), above 11 years of education (53.1%) (p = 0.200) and belonging to middle class (67.1%) (p = 0.909).