OBJECTIVES: Anti-diabetics have varying efficacy and safety profiles. This study aimed to better understand patient preferences for oral anti-diabetics by examining the relative importance (RI) of medication attributes that influence treatment selection among patients in the US with type 2 diabetes mellitus (T2DM).   METHODS: A web-based discrete choice experiment (DCE) was developed to assess the RI of 7 medication attributes (effectiveness, hypoglycemia, weight change, gastrointestinal/nausea side effects [SE], urinary tract infections [UTI]/genital infection SEs, blood pressure change, and cardiovascular risk). Participants were presented with 2 hypothetical medications composed of varying levels of each attribute and asked to select the preferred profile. Part-worth utility values, or preference weights, were calculated to provide information on the extent to which participants preferred one level of an attribute over another and used to derive RI values. RI values were calculated based upon the relative weight of each attribute in the sum of part-worth utility values, with higher values indicating greater importance. RESULTS: A total of 809 invitations were sent; 54% responded. The final sample was composed of the first 200 eligible participants with self-reported T2DM (50% male, mean age 60.9 years). The RI values for the attributes in order of importance were effectiveness (25.9%), hypoglycemic events (21.5%), weight change (21.0%), gastrointestinal/nausea SEs (14.1%), UTI/genital infection SEs (11.0%), blood pressure (3.7%), and cardiovascular risk (2.9%). Effectiveness, hypoglycemic events, and weight change comprised 68.4% of the RI. CONCLUSIONS: Results suggest that effectiveness, hypoglycemic events, and weight change are the predominant influences on patients’ medication decisions for T2DM. These results were consistent with findings from a DCE conducted in the United Kingdom (UK), which utilized a similar methodology and yielded similar RI results. The confluence of these findings highlights the importance of these attributes as drivers of medication decisions in patients with T2DM in the United States and UK.