A related commentary discusses this research. Cardiovascular disease (CVD) is the leading cause of death among patients with end-stage kidney disease who are undergoing haemodialysis, yet many standard cardioprotective therapies have not been effective in reducing CVD in this patient population. Based on observations from the past 2 decades, deficiency of active vitamin D has been a prime candidate for CVD reduction. This study however demonstrated no benefit. Ultimately, this trial helps fill a wide gap in end stage kidney disease (ESKD) evidence. Combined with the similar lack of benefit of vitamin D receptor agonists (VDRAs) on cardiovascular surrogates in patients with advanced, predialysis CKD, the current evidence does not support use of VDRAs in patients with ESKD and relatively low parathyroid hormone (PTH) to prevent CVD. However, given the inherent complexity of mineral metabolism physiology, it is always possible to question whether the intervention is delivered too early, too late, with the wrong co-interventions, or to the wrong patient. Scientifically, this trial is a reminder that VDRAs are far more complex than the 1-dimensional windows of PTH reduction through which these agents are typically viewed. Further, results of the trial may even warn of the potential for some harm associated with use of these drugs. These results emphasise the need for dialysis studies that are large enough and have adequate retention and adherence to ensure precise treatment effects can be obtained.