Bacterial cold water disease (BCWD) causes significant mortality and economic losses for the global rainbow trout aquaculture industry. Currently, there is no effective commercially available vaccine for the disease caused by Flavobacterium psychrophilum (Fp). For the past 20 years, the USDA-ARS injection challenge model has successfully used a single strain (CSF-259-93) of the pathogenic Fp bacteria for selective breeding of resistant rainbow trout and to characterize the genetic architecture of BCWD resistance in commercial US breeding populations. Previously, we identified similar genetic architecture in two important commercial rainbow trout populations with strong QTLs for survival response on chromosomes Omy8 and Omy25p (OmyA31) and another large-effect QTL that was detected on Omy3 only in one of the two populations. The objectives of this study were to (1) characterize the genetic architecture of resistance to BCWD in a third important commercial US breeding population (TLUN= Troutlodge, Inc. November-spawning breeding population) using our standard Fp strain (CSF-259-93); (2) evaluate the genetic architecture of resistance to a novel Fp strain (ARS-037-11) in the TLUN breeding population; and (3) estimate the heritability and genetic correlation of resistance to BCWD inflicted by the two Fp strains. Offspring from 108 TLUN 2018 year-class full-sib families were challenged with one of the two strains in 3 replicate tanks. Offsprings from one tank per challenge (N= 2073) were genotyped using whole-genome sequencing (WGS) at low genome coverage (~1x) and genotypes from 4.6M SNP were imputed in the population using data from high coverage WGS (>10x) of the parents. Heritability was moderate with estimates of 0.45-0.53 and 0.37-0.46 for the novel and standard Fp strains, respectively, and the genetic correlation was low-moderate (0.19-0.36). Three moderate-large effect QTLs with additive genetic variance (AGV) of 2%-22% were detected on chromosomes Omy3, 5 and OmyA31 for resistance to the novel Fp strain, and 10 moderate-effect QTLs (AGV= 2-10%) were detected on chromosomes Omy3, 8, 13, 17, 20, 24, 25q and OmyA31 for the standard Fp strain. The most notable difference was a new large-effect QTL (AGV= 22%) for resistance to the novel Fp strain that was detected on chromosome Omy5. Our findings suggest that (1) resistance to BCWD can be improved through selective breeding in this important commercial breeding population; (2) the genetic architecture of resistance to BCWD caused by either Fp strain is oligogenic which can be exploited for marker assisted selection; (3) the low genetic correlation and the unique QTLs detected for resistance to each Fp strain suggest that selective breeding for multiple Fp strains should be considered when breeding for BCWD resistance; and (4) the high density SNP panel used in the GWAS enabled finer profiling of SNP effects within narrower QTL regions.