This paper presents an empirical investigation into several performance measures for operational analysis on two-lane highways. The performance measures investigated are average travel speed, average travel speed to free-flow speed, percent followers, followers flow, followers density, percent impeded, impeded flow, and impeded density. Field data from 16 study sites in the states of Montana, Idaho, Oregon, and North Carolina representing Class 1, Class 2, and Class 3 highways were used in this study. The level of association between performance measures and some of the most important traffic variables was examined with graphical and statistical techniques. The traffic variables investigated in this study included combined flow in both directions of travel; proportion of traffic in the direction of travel, called in this study “traffic split”; percentage of heavy vehicles; and speed variance. Study results suggest that speed-related measures have weak associations with traffic variables compared with headway-related measures. Further, compound measures involving headway and traffic flow or density exhibited the highest associations with traffic variables. With regard to two-lane highway type, higher associations are exhibited at Class 1 sites compared with Class 2 and Class 3 sites. Performance measures showed the highest associations with combined flow and traffic split.