Background: Hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) are oral alternatives to current standard-of-care treatments for anaemia in chronic kidney disease (CKD). We conducted network meta-analyses to indirectly compare clinical outcomes for three HIF-PHIs in dialysis and non-dialysis populations with anaemia in CKD., Methods: The evidence base comprised phase III, randomised, controlled trials evaluating daprodustat, roxadustat, or vadadustat. Three outcomes were evaluated: efficacy [change from baseline in haemoglobin (Hgb)], cardiovascular safety [time to first major adverse cardiovascular event (MACE)] and quality of life [change from baseline in 36-Item Short Form Health Survey (SF-36) Vitality score]. Analyses were performed separately for all patients and for erythropoiesis-stimulating agent (ESA) non-users at baseline (non-dialysis population) or prevalent dialysis patients (dialysis population). Bayesian Markov Chain Monte Carlo methods with non-informative priors were used to estimate the posterior probability distribution and generate pairwise treatment comparisons. Point estimates (medians of posterior distributions) and 95% credible intervals (CrI) were calculated., Results: Seventeen trials were included. In non-dialysis patients, there were no clinically meaningful differences between the three HIF-PHIs with respect to Hgb change from baseline [all patients analysis (total n = 7907): daprodustat vs. roxadustat, 0.09 g/dL (95% CrI -0.14, 0.31); daprodustat vs. vadadustat, 0.09 g/dL (-0.04, 0.21); roxadustat vs. vadadustat, 0.00 g/dL (-0.22, 0.22)] or risk of MACE [all patients analysis (total n = 7959): daprodustat vs. roxadustat, hazard ratio (HR) 1.16 (95% CrI 0.76, 1.77); daprodustat vs. vadadustat, 0.88 (0.71, 1.09); roxadustat vs. vadadustat, 0.76 (0.50, 1.16)]. Daprodustat showed a greater increase in SF-36 Vitality compared with roxadustat [total n = 4880; treatment difference 4.70 points (95% CrI 0.08, 9.31)]. In dialysis patients, Hgb change from baseline was higher with daprodustat and roxadustat compared with vadadustat [all patients analysis (total n = 11 124): daprodustat, 0.34 g/dL (0.22, 0.45); roxadustat, 0.38 g/dL (0.27, 0.49)], while there were no clinically meaningful differences in the risk of MACE between the HIF-PHIs [all patients analysis (total n = 12 320): daprodustat vs. roxadustat, HR 0.89 (0.73, 1.08); daprodustat vs. vadadustat, HR 0.99 (0.82, 1.21); roxadustat vs. vadadustat, HR 1.12 (0.92, 1.37)]. Results were similar in analyses of ESA non-users and prevalent dialysis patients., Conclusions: In the setting of anaemia in CKD, indirect treatment comparisons suggest that daprodustat, roxadustat, and vadadustat are broadly clinically comparable in terms of efficacy and cardiovascular safety (precision was low for the latter), while daprodustat may be associated with reduction in fatigue to a greater extent than roxadustat., Competing Interests: A.S. is an employee of GSK. R.D.L. has received research support from Bristol Myers Squibb, GSK, Medtronic, and Pfizer; and consulting fees from Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi-Sankyo, GSK, Medtronic, Merck, Pfizer, and Portola. C.P.K. has received consulting fees from Abbott, Akebia, AstraZeneca, Bayer, Boehringer Ingelheim, Cara Therapeutics, CSL Behring, CSL Vifor, GSK, Pharmacosmos, ProKidney, Rockwell, Takeda, and Tricida, outside of the submitted work. A.C. has received research grants from CSL Vifor; consultancy fees from Astellas, AstraZeneca, Boehringer Ingelheim, CSL Vifor, GSK, Novo Nordisk, and Otsuka; speaker fees from Amgen, Astellas, AstraZeneca, Bayer, CSL Vifor, GSK, Novo Nordisk, and Sanofi (Mexico) and travel support from Astellas, AstraZeneca, and GSK, outside the submitted work. AC is also a member of the Catalan Registry of Renal Patients (RMRC). S.A.M was an employee of GSK at the time of the study. N.B. is an employee of, and shareholder in, GSK. T.J.K. is an employee of, and shareholder in, GSK. V.G.-H. is an employee of Analysis Group, Inc., which received funding from GSK to conduct this research. R.A. is an employee of Analysis Group, Inc., which received funding from GSK to conduct this research. R.R.C. is an employee of and shareholder in GSK. K.L.J. has received consulting fees from GSK, Vifor, and Akebia. A.J.S. has received consultancy fees from Analysis Group, Inc. I.D. has received research grants from Sanofi, NIHR Clinical Research Network (West Midlands, UK), and Kidney Research UK; and honoraria for advisory boards and speaker meetings from GSK, AstraZeneca, Sanofi, and Vifor., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)