Abstract Background Low cardiorespiratory fitness (V̇O 2peak ) is highly associated with chronic disease and mortality from all causes. Whilst exercise training is recommended in health guidelines to improve V̇O 2peak , there is considerable inter-individual variability in the V̇O 2peak response to the same dose of exercise. Understanding how genetic factors contribute to V̇O 2peak training response may improve personalisation of exercise programs. The aim of this study was to identify genetic variants that are associated with the magnitude of V̇O 2 peak response following exercise training. Methods Participant change in objectively measured V̇O 2 peak from 18 different interventions was obtained from a multi-centre study (Predict-HIIT). A genome-wide association study was completed (n = 507), and a polygenic predictor score (PPS) was developed using alleles from single nucleotide polymorphisms (SNPs) significantly associated ( P 0.1). Significant correlations were found for beta coefficients of variants in the Predict-HIIT ( P < 1 × 10 –4 ) and the validation study ( P < × 10 –6 ), indicating that general effects of the loci exist, and that with a higher statistical power, more significant genetic associations may become apparent. Conclusions Ongoing research and validation of current and previous findings is needed to determine if genetics does play a large role in V̇O 2 peak response variance, and whether genomic predictors for V̇O 2 peak response trainability can inform evidence-based clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (ANZCTR), Trial Id: ACTRN12618000501246, Date Registered: 06/04/2018, http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=374601&isReview=true .