This study examines recent trends and factors in school dropout at the upper secondary education level across Latin America. The methodology employs repeated cross sections of data to track the life cycle path of cohorts of individuals in 18 countries. A key finding is that while upper secondary enrollment rates increased in the region, dropout has remained persistently high, despite relatively favorable macroeconomic conditions. To explain dropout trends, the study examines the impact of three groups of factors: (i) shifts in the cohort size and socioeconomic composition of the population eligible for entering upper secondary; (b) the macroeconomic environment and labor market opportunities; and (c) the returns to schooling. We show that an important factor in persistently high dropout rates has been the higher numbers of students from poor socioeconomic backgrounds reaching upper secondary. In addition, high returns to education have been a pull factor into schooling, while, especially in countries where the majority of youth dropout prior to upper secondary, the data confirm an apparent substitution effect due to the opportunity cost of forgoing employment opportunities. The findings confirm the growing policy focus on upper secondary across Latin America and suggest implications for the policy agenda.