Objectives: To quantify the association between complementary and alternative medicine (CAM) use and quality of life in a population with type 2 diabetes and/or cardiovascular disease, accounting for demographics, socioeconomic status, health and lifestyle factors. Design and setting: Data are from a purpose-designed survey of 2915 individuals aged 18 years and over, all with type 2 diabetes and/or cardiovascular disease (CVD), collected in 2010. Key variables are compared for comparability with nationally representative data. It was hypothesised that CAM use would be associated with higher quality of life, as measured by the Assessment of Quality of Life-4 dimension (AQoL-4D) instrument. Three key variables are used for CAM use in the previous twelve months. In the robustness analysis, CAM use is further disaggregated into the types of practitioner or product used, the frequency of use, the reason for use and expenditure on CAM. Results: CAM use is not associated with higher QoL for this sub-population, and in fact intensive use of CAM practitioners is associated with significantly lower QoL. Conclusions: It is important not to assume that patients have sufficient information with which to make optimal choices regarding CAM use in the absence of accessible and relevant evidence based guidance.