We examined the relationships between xylem resistance to cavitation and 16 structural and functional traits across eight unrelated Populus deltoides×Populus nigra genotypes grown under two contrasting water regimes. The xylem water potential inducing 50% loss of hydraulic conductance (Ψ₅₀) varied from −1.60 to −2.40 MPa. Drought‐acclimated trees displayed a safer xylem, although the extent of the response was largely genotype dependant, with Ψ₅₀ being decreased by as far as 0.60 MPa. At the tissue level, there was no clear relationship between xylem safety and either xylem water transport efficiency or xylem biomechanics; the only structural trait to be strongly associated with Ψ₅₀ was the double vessel wall thickness, genotypes exhibiting a thicker double wall being more resistant. At the leaf level, increased cavitation resistance was associated with decreased stomatal conductance, while no relationship could be identified with traits associated with carbon uptake or bulk leaf carbon isotope discrimination, a surrogate of intrinsic water‐use efficiency. At the whole‐plant level, increased safety was associated with higher shoot growth potential under well‐irrigated regime only. We conclude that common trade‐offs between xylem resistance to cavitation and other physiological traits that are observed across species may not necessarily hold true at narrower scales.