Background and Aims. Complementary and alternative medicine (CAM) use among patients with inflammatory bowel disease (IBD) is common. The aim of this study was to explore associations between CAM use and health-related quality of life (HRQoL) as well as identifying whether sociodemographic factors, disease activity, and personal resources (self-efficacy) influence HRQoL scores in users and nonusers of CAM. Methods. Measures included sociodemographic and disease-related data, the International-CAM Questionnaire, and General Self-Efficacy Scale. A univariate analysis of variance was used to assess the association between CAM use and HRQoL. The associations between clinical, demographic, and personal factors and HRQoL were examined through linear regression analyses. Results. CAM users had statistically significant lower SF-36 scores compared to nonusers and the background population. Nonusers scored significantly lower compared to the background population in two out of the eight SF-36 dimensions. Independent of CAM use, disease activity had a negative impact and self-efficacy had a positive impact on HRQoL. Conclusions. HRQoL in CAM users with IBD was significantly lower compared to nonusers and the background population. Independent of CAM use, disease activity was negatively associated with HRQoL. Self-efficacy had a positive impact on the mental health dimensions in both CAM users and nonusers.