Previous studies documented that a uniform design speed does not necessarily guarantee design consistency on rural two-lane facilities. Since a similar process is also followed for four-lane rural highways, it is reasonable to assume that similar inconsistencies could be found on such roadways. The operating speed-based method has been extensively used in other countries as the primary method to examine design consistency. Numerous studies have been completed on rural two-lane highways for predicting operating speeds and evaluating design consistency. However, few studies have considered these issues for rural four-lane highways. Therefore, prediction models for rural four-lane highways are needed. This study aims to develop models to predict operating speeds on horizontal curves of rural four-lane highways. A parallel study documented that speeds on inside and outside lanes are different; therefore, two multiple linear regression models are developed. For the inside lane, the significant factors are shoulder type, median type, pavement type, approaching section grade, and horizontal curve length. For the outside lane, factors include shoulder type, median type, approaching section grade, presence of approaching curve, and curve radius and length. The factors in the two models indicate that the curve itself mainly influences a driver's speed choice. The models were validated by using the data-splitting approach, and validation shows that there are no statistical differences between the predicted and field-observed operating speeds.