Research has thoroughly examined various factors that are related to university student persistence. Studies suggest that a multitude of characteristics are predictive of student success, and theory supports examining these characteristics at the institutional level. However, few studies utilise robust, single-institution samples using a holistic framework. The purpose of this study was to use a comprehensive framework to examine academic, psychosocial, noncognitive, and other background factors that are related to retention at one large, public four-year institution in the southeastern United States. Data for 12,342 students were drawn from multiple sources, and hierarchical generalised linear models were used to identify important predictors of retention both before beginning university and after the first semester. Findings from the study showed that a variety of pre-university factors such as high school performance, institutional fit, and financial scholarships were significant predictors of retention both before and after the first semester. Notably, these important variables were distributed across the categories of the comprehensive framework. Results also revealed moderated relationships between several variables with factors such as ethnicity and first-generation status. The results of this study have important implications for higher education policymakers, administrators, and researchers in terms of variable selection and measurement in predictive retention models for beginning university students.