Prostate cancer is reliant on androgen signalling for survival, hence current treatments target this reliance via androgen deprivation or anti-androgen therapies. While these treatments are initially effective, resistance is inevitable, highlighting a need for new treatments for men with prostate cancer. Genomic studies have highlighted dysregulation of the cell cycle as a major driver of prostate cancer progression. Cell cycle inhibitors, including the CDK4/6 inhibitor ribociclib, are clinically approved for metastatic breast cancer and are in clinical trials for prostate cancer, but resistance to these therapies is becoming a major clinical problem. In addition to regulating the cell cycle, there is evidence that CDK4/6 influences lipid metabolism. This may be critical to the clinical translation of CDK4/6 inhibitors in prostate cancer, given that altered lipid metabolism is associated with poor prognosis. The aim of this study was to characterise adaptive resistance to ribociclib and understand lipid metabolism changes that could potentially contribute to resistance in prostate cancer. To achieve this, we generated ribociclib resistant LNCaP prostate cancer cells through dose escalation passage to a clinically relevant dose of 500nM. Ribociclib-resistant cells displayed no significant delay in growth or proliferation compared to parental LNCaP cells. Characterization of key cell cycle markers revealed increased gene and protein expression of cyclin-D1 and phosphorylation of Rb-1 in the resistant cells compared to parental cells. We then performed mass-spectrometry based lipidomic profiling on ribociclib-resistant cells, revealing an increase in abundance and elongation of phosphatidylcholine and phosphatidylethanolamine phospholipids compared to parental cells. QRT-PCR analysis of ELOVL elongase enzymes displayed increases in the androgen regulated ELOVL2,5 and 7 genes, while there were no significant changes in fatty acid oxidation or synthesis pathways compared to parental cells. Given that our team has previously demonstrated lipid elongation is a pro-survival pathway in prostate cancer, this research has revealed a metabolic vulnerability associated with CDK4/6 inhibitors that may drive resistance to these agents.