Recent advances in flexible pavement design have prompted agencies to move toward the development and use of mechanistic-empirical (M-E) design procedures. The purpose of this paper is to analyze seasonal trends in flexible pavement layer moduli in order to calibrate a mechanistic-empirical design procedure specific to Minnesota. The relationships investigated were between climate factors, surface and subsurface conditions, and pavement material properties. The results presented focus on the base and subgrade layers and show that the layer moduli vary with the state of moisture in the pavement. The data used to develop this approach were collected from four flexible pavement Long Term Pavement Performance Seasonal Monitoring Program sites (LTPP SMP) and the Minnesota Road Research Project (Mn/ROAD). Temperature data are used in this study to characterize the severity of a winter and to approximate the onset of freezing and thawing cycles. Finally, seasonal trends in pavement layer moduli were quantified for use in an M-E design of flexible pavements.