Spain’s population of people aged 100 years and over has increased tenfold since the last quarter of the 20th century, exceeding 16,000 individuals by 2019. Despite this cohort’s growth, which has made centenarians a significant segment of Spain’s population in their own right, centenarians have remained little studied from the perspective of social sciences. A key challenge for research concerning centenarians is understanding their personal experiences of reaching this landmark age; such information could help to identify the sociodemographic and psychosocial factors that enable people to live such extraordinarily long lives. Given this context, the present article describes the research protocol followed in the projects SeviCent – Sevilla Centenarian Study and C&LCent – Castilla y León Centenarian Study, which are mainstream qualitative studies of people aged 100 years and over who reside in the regions with the lowest and highest life expectancy in Spain, respectively. The general aim of these studies was to analyze, through semi-structured interviews conducted between 2018 and 2019 that were based on a biographical and life-cycle approach, the physical, social, and emotional wellbeing of a cohort of centenarians who had no cognitive impairments. Specifically, based on the experiences of applying this protocol, the present study describes the methodological considerations—research design, sampling, interview script, indicators, fieldwork, and analysis plan—that should be included in future qualitative, social sciences–focused studies concerning very old people for whom the population segment is scarce, scattered, and fragile.