Chemical, cultural, and biological methods have been developed to control leafy spurge in a variety of environments. Aphthona spp. biological control agents have established throughout the northern Great Plains and Rocky Mountain region and successfully controlled leafy spurge in many areas, but notable exceptions include areas with sandy soils. Leafy spurge control can be improved by combining methods such as chemical, biological, or cultural treatments, compared to a single method used alone. The effects of Aphthona spp., imazapic herbicide, and interseeded native grass species alone or in combination for leafy spurge control were evaluated at two locations in southeastern North Dakota for 5 yr. Both the Sheyenne National Grassland (SNG) and Walcott, ND, study locations had greater than 80% sand soil. Leafy spurge stem density, canopy cover, and yield were reduced for 1 to 2 yr in all treatments that included imazapic, with no difference in control between single and combination treatments. Aphthona spp. and interseeded native grasses alone or combined did not reduce leafy spurge density or cover. Aphthona spp. population remained low throughout the study at both locations. Forb yield increased during the study at the SNG but not the Walcott location. Conversely, warm-season grass yield increased at Walcott but not at the SNG. Leafy spurge stem density declined from 92 to 50 stems/m2 in 5 yr at the SNG site. The decline could not be attributed to specific treatments applied in this study and may be due to self-limitation or soil pathogens.