Using U-turns as alternatives to direct left-turns is an important access management treatment which has been widely implemented in the United States to improve safety on multilane highways. The primary objective of this study is to evaluate the safety effects of the separation distances between driveway exits and downstream U-turn locations. To achieve the research objective, crash data reported at 140 street segments in the state of Florida were investigated. The selected sites were divided into three groups based on the separation distances. t-Tests and proportionality tests were performed for comparing crash frequency, crash type, and crash severity between different separation distance groups. Negative-binomial models were developed for examining the factors that contribute to the crashes reported at selected sites. The data analysis results show that the separation distances significantly impact the safety of the street segments between driveways and downstream U-turn locations. A 10% increase in separation distance will result in a 3.3% decrease in total crashes and a 4.5% decrease in the crashes which is related with right-turns followed by U-turns. The models also show that providing U-turns at a signalized intersection will result in more crashes at weaving sections. Thus, if U-turns are to be provided at a signalized intersection, a longer separation distance shall be provided.