Objective Compare changes in lipids and lipid-associated cardiovascular (CV) risk markers in patients with rheumatoid arthritis (RA) treated with tocilizumab or adalimumab. Methods Post-hoc analysis was performed in patients with RA who received tocilizumab intravenously every 4weeks or adalimumab subcutaneously every 2weeks for 24weeks in the ADACTA trial. Lipid and lipid-associated CV risk biomarkers, including high-density lipoprotein-associated serum amyloid-A (HDL-SAA), secretory phospholipase A(2) IIA (sPLA(2) IIA) and lipoprotein(a) (Lp(a)), were measured at baseline and at week 8. Results The study included 162 patients treated with tocilizumab and 162 patients treated with adalimumab; HDL-SAA and sPLA(2) IIA were measured in a subpopulation of 87 and 97 patients, respectively. Greater increases in mean low-density lipoprotein cholesterol (LDL-C) (0.46mmol/L (95% CI 0.30 to 0.62)), high-density lipoprotein cholesterol (HDL-C) (0.07mmol/L (0.001 to 0.14)), total cholesterol (TC) (0.67mmol/L (0.47 to 0.86)), triglycerides (0.24mmol/L (0.10 to 0.38)) and TC:HDL ratio (0.27 (0.12 to 0.42)) occurred with tocilizumab from baseline to 8weeks. HDL-SAA, sPLA(2) IIA and Lp(a) decreased more with tocilizumab than adalimumab. Median changes from baseline to week 8 were -3.2 and -1.1mg/L (p=0.0077) for HDL-SAA and -4.1 and -1.3ng/mL (p<0.0001) for sPLA(2) IIA; difference in adjusted means was -7.12mg/dL (p<0.0001) for Lp(a). Similar results were observed in efficacy responders and non-responders per American College of Rheumatology and European League against Rheumatism criteria. Conclusion LDL-C and HDL-C increased more with tocilizumab than adalimumab. HDL-SAA, sPLA(2) IIA and Lp(a) decreased more with tocilizumab. Lipid change effects of interleukin-6 and tumour necrosis factor (TNF) inhibition, manifest by their net impact on lipids and lipoproteins, are not synonymous; the clinical significance is unclear and requires further study. Trial registration number NCT01119859.; post-results