Tributylphosphine is prepared industrially by the hydrophosphination of phosphine with 1-butene: the addition proceeds by a free radical mechanism, and so the Markovnikov rule is not followed.

For example, benzyl chloride gives a phosphonium salt (here tributyl(phenylmethyl)phosphonium chloride):[2] Tributylphosphine is a common ligand for the preparation of complexes of transition metals in low oxidation states.

Compared to other tertiary phosphines, it is compact (cone angle: 136°) and basic (χ-parameter: 5.25 cm−1)[3] Tributylphosphine finds some industrial use as a catalyst modifier in the cobalt-catalyzed hydroformylation of alkenes, where it greatly increases the ratio of straight-chain aldehydes to branched-chain aldehydes in the product mixture.

[2] Although tributylphosphine is generally regarded as toxic, its biological effects can be manipulated by drug delivery strategies.

For example, a photoactivatable version of tributylphosphine has been used to induce disulfide bond cleavage and reductive stress in living cells.