Weak multivalent interactions govern a large variety of biological processes like cell–cell adhesion and virus–host interactions. These systems distinguish sharply between surfaces based on receptor density, known as superselectivity. Present experimental studies typically involve tens or hundreds of interactions, resulting in a high entropic contribution leading to high selectivities. However, if, and if so how, systems with few ligands, such as multi-domain proteins and bacteriophages binding to their host, show superselective behavior is an open question. Here, we address this question with a multivalent experimental model system based on star shaped branched DNA nanostructures (DNA nanostars) with each branch featuring a single stranded overhang that binds to complementary receptors on a target surface. Each DNA nanostar possesses a fluorophore, to directly visualize DNA nanostar surface adsorption by total internal reflection fluorescence microscopy (TIRFM). We observe that DNA nanostars can bind superselectively to surfaces and bind optimally at a valency of three, for a given binding strength and concentration. We explain this optimum by extending the current theory with interactions between DNA nanostar binding sites (ligands). Our results add to the understanding of multivalent interactions, by identifying cooperative mechanisms that lead to optimal selectivity, and providing quantitative values for the relevant parameters. These findings inspire additional design rules which improve future work on selective targeting in directed drug delivery.@en