BACKGROUND: Often affecting knee joints, osteoarthritis (OA) is the most common type of arthritis and by 2020 is predicted to become the fourth leading cause of disability globally. Without cure, medication management is symptomatic, mostly with simple analgesics such as acetaminophen and non-steroidal anti-inflammatory drugs (NSAIDs), and glucosamine sulfate. Adherence to arthritis medications is generally low. Intentional non-adherence, that is deliberate decision-making about the use of analgesics, occurs in OA patients. To date, a limited number of studies have explored medication-taking decisions in people with OA nor the extent to which individuals' trade off one treatment factor for another in their decision-making using quantitative techniques. This study aimed to estimate the relative influence of medication-related factors and respondent characteristics on decisions to continue medications among people with symptomatic OA. METHODS: A discrete choice experiment (DCE) was conducted among participants attending end-of-study visits in the Long-term Evaluation of Glucosamine Sulfate (LEGS) study (ClinicalTrials.gov ID: NCT00513422). The paper-based survey was used to estimate the relative importance of seven medication specific factors (pain efficacy, mode of action, dose frequency, treatment schedule, side effects, prescription, and out-of-pocket costs) and respondent characteristics on decisions to continue medications. RESULTS: 188 (response rate 37%) completed surveys were returned. Four of the seven medication factors (side effects, out-of-pocket costs, mode of action, treatment schedule) had a significant effect on the choice to continue medication; patient characteristics did not. Assuming equivalent pain efficacy and disease-modifying properties for glucosamine, the positive relative likelihood of continuing with sustained-release acetaminophen was equivalent to glucosamine. By contrast, the negative relative likelihood of NSAID continuation was mostly driven by the side effect profile. The predicted probability of continuing with glucosamine decreased with increasing out-of-pocket costs. CONCLUSIONS: This study has characterised the complexity of medication-taking decisions that potentially underpin intentional non-adherent behaviour for people with symptomatic OA. In particular, medication risks and cost were important and ought to be borne into considerations in interpreting clinical trial evidence for practice. Ultimately addressing these factors may be the way forward to realising the full potential of health and economic benefits from the efficacious and safe use of OA medications.