Resistance to Aphis gossypii in Cucumis melo has been largely studied but A. gossypii variability has never been considered. Resistance to colonization by A. gossypii, clone NM1, and to non persistent virus transmission by this clone is conferred by a NBS-LRR gene called Vat, isolated in the PI 161375 accession. We investigated resistance to A. gossypii with four clones of A. gossypii that belong to two very distinct genotypes, NM1 and C9. The Vat gene conferred a high level of resistance to a NM1 clone and partial resistance to a C9 clone. Four additive QTL and two pairs of epistatic QTL were detected in a recombinant inbred line population derived from the cross ‘Védrantais’ x PI 161375. Half of them clearly have a specific effect on the acceptance by NM1 or C9 genotypes. We observed transgressive lines more resistant to NM1 or C9 in our RIL populations than PI 161375. Moreover, we studied resistance to A. gossypii and to virus transmission by A. gossypii in a set of 21 C. melo accessions. All the accessions resistant to virus transmission by C9 A. gossypii were resistant to virus transmission by NM1 genotype, and most of them were resistant to acceptance and colonization by the NM1 genotype. This is the phenotype of PI 161375, and we hypothesized that these phenotypes were controlled by the Vat gene. Other phenotypes were observed: resistance to NM1 A. gossypii (aphids and virus transmission) and susceptibility to C9 A. gossypii (aphids and virus transmission), independence between aphid resistance and resistance to virus transmission when using the same clone of A. gossypii. These phenotypes may be conferred by the locus Vat (different alleles) or by other locus of aphid resistance.