This study develops a target setting methodology for the (Moving Ahead for Progress) MAP-21 Interstate Travel Time Reliability Measure of “Percent of the Person-Miles Traveled on the Interstate that are Reliable” (PMTR-IS). The study uses data specific to Virginia for a set of independent variables (Hourly Volume, and Volume/Capacity Ratio, Truck Percentage, Equivalent Property Damage Only Rate, Lane Impacting Incident Rate, Number of Lanes, Presence of Safety Service Patrol, Terrain, Urban Designation) to predict whether a MAP-21 reporting segment is reliable. This is used to estimate predicted PMTR-IS with the MAP-21 specified formula. CART (classification and regression trees) models were used with 1,536 different configurations. Of the four best performing models, one was selected using engineering judgement. Datasets from 2017 and 2018 were used for training, and from 2019 and 2020 for testing. The predicted and calculated PMTR-IS were compared, and the error percentage was lower than 1% for 2019, which can be considered negligible. The 2020 error rate was higher and can perhaps be attributed to unusual reliability because of the impacts of the pandemic on travel. Sensitivity analyses revealed that the predicted PMTR-IS is reactive to capacity increase in unreliable sections at a local level, slower to respond to local AADT (annual average daily traffic) increase, and stable to small statewide AADT oscillations. The authors recommend using this methodology for target setting, taking into consideration the state authorities’ other strategic priorities.