This dataset contains the LC-MS/MS raw files generated during the characterisation of lysine lactylation on mouse RIPK3 (UniProt Q9QZL0) in the context of necroptosis. Four raw files from three independent mass spectrometry experiments are included. Experiment 1 (subproject XC06946PRM): targeted analysis of the product of an in vitro lactylation reaction, in which purified His-tagged RIPK3 kinase domain was incubated with recombinant Flag-PCAF in the presence of lactyl-CoA and ATP. The reaction product was submitted as a protein solution and digested in solution. Peptides were separated on an EASY-nLC 1200 UPLC system and analysed on an Orbitrap Exploris 480 mass spectrometer in parallel reaction monitoring mode, and tandem mass spectra were searched with MaxQuant v1.6.15.0 against the mouse RIPK3 sequence. Experiment 2 (subproject XD01013PRM): targeted analysis of endogenous RIPK3. L929 mouse fibroblasts were treated with TNF-alpha together with the pan-caspase inhibitor z-VAD-fmk to induce necroptosis, nuclear fractions were enriched by subcellular fractionation, endogenous RIPK3 was immunoprecipitated from the nuclear lysate using an anti-RIPK3 antibody, and the bead-bound material was digested on-bead. Peptides were separated on a Vanquish Neo UPLC system and analysed on an Orbitrap Astral mass spectrometer, and tandem mass spectra were searched with MaxQuant v1.6.15.0 against the mouse RIPK3 sequence. Experiment 3 (subproject XC07843LI, samples G1 and G2): data-dependent acquisition (DDA) analysis of endogenous RIPK3 immunoprecipitates prepared as described for Experiment 2, from untreated L929 cells (G1) and from TNF-alpha/z-VAD-treated L929 cells (G2). Peptides were analysed on an Orbitrap Exploris 480 mass spectrometer equipped with a FAIMS Pro interface, and tandem mass spectra were searched with Proteome Discoverer 2.4 against a single-entry database containing the mouse RIPK3 sequence. Targeted analyses were performed to monitor lactylated forms of the RIPK3 tryptic peptide ISWEVKAMVNLR. The methionine-oxidised form (precursor m/z 767.4083, 2+) was detected in the endogenous immunoprecipitate (XD01013PRM), and the form without methionine oxidation (precursor m/z 759.4109, 2+) was detected in the in vitro reaction product (XC06946PRM_B1).