Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. ; Background: Limited evidence exists regarding the relationship between health literacy and health-related quality of life (HRQoL) in Australian patients from primary care. The objective of this study was to investigate the impact of health literacy on HRQoL in a large sample of patients without known vascular disease or diabetes and to examine whether the difference in HRQoL between low and high health literacy groups was clinically significant. Methods: This was a cross-sectional study of baseline data from a cluster randomised trial. The study included 739 patients from 30 general practices across four Australian states conducted in 2012 and 2013 using the standard Short Form Health Survey (SF-12) version 2. SF-12 physical component score (PCS-12) and mental component score (MCS-12) are derived using the standard US algorithm. Health literacy was measured using the Health Literacy Management Scale (HeLMS). Multilevel regression analysis (patients at level 1 and general practices at level 2) was applied to relate PCS-12 and MCS-12 to patient reported life style risk behaviours including health literacy and demographic factors. Results: Low health literacy patients were more likely to be smokers (12 % vs 6 %, P = 0.005), do insufficient physical activity (63 % vs 47 %, P