Background Bacterial fruit blotch (BFB), a disease caused by Acidovorax citrulli , results in significant economic losses in melon. The causal QTLs and genes for resistance to this disease have yet to be identified. Resistance ( R )-genes play vital roles in resistance to plant diseases. Since the complete genome sequence of melon is available and genome-wide identification of R -genes has been performed for this important crop, comprehensive expression profiling may lead to the identification of putative candidate genes that function in the response to BFB. Results We identified melon accessions that are resistant and susceptible to BFB through repeated bioassays and characterized all 70 R -genes in melon, including their gene structures, chromosomal locations, domain organizations, motif distributions, and syntenic relationships. Several disease resistance-related domains were identified, including NBS, TIR, LRR, CC, RLK, and DUF domains, and the genes were categorized based on the domains of their encoded proteins. In addition, we profiled the expression patterns of the genes in melon accessions with contrasting levels of BFB resistance at 12 h, 1 d, 3 d, and 6 d after inoculation with A. citrulli via qRT-PCR. Six R -genes exhibited consistent expression patterns (MELO3C023441, MELO3C016529, MELO3C022157, MELO3C022146, MELO3C025518, and MELO3C004303), with higher expression levels in the resistant vs. susceptible accession. Conclusion We identified six putative candidate R -genes against BFB in melon. Upon functional validation, these genes could be targeted for manipulation via breeding and biotechnological approaches to improve BFB resistance in melon in the future.