OBJECTIVES: Although the ability to interact with patients in an on-line environment has expanded substantially over the past few years, many researchers are concerned that participants may not be representative from a medication experience perspective (i.e., biased towards complainers). The purpose of this study is to investigate patient responses on treatment satisfaction using a validated PRO measure, the Treatment Satisfaction Questionnaire for Medications (TSQM), collected through a survey of patients with depression from an on-line community. METHODS: A random sample of iGuard.org members treated with an antidepressant were invited to complete an online version of the TSQM, a widely used validated 14-item generic treatment satisfaction instrument.  iGuard.org is an online patient community that provides a free medication monitoring service to patients. Non-parametric item response analyses were performed to determine the relationship between scores on individual items and total TSQM scores. RESULTS: Responses from 3641 patients were included in the analyses. TSQM Global Satisfaction scores ranged from 0 – 100 suggesting a broad spectrum of treatment satisfaction. Non-parametric Item Response analyses of raw scores revealed that individual items of the TSQM discriminated differences in patient satisfaction. That is, as total scores increased the probability of low scores on the individual items decreased and the probability of higher scores increased. As expected, patient satisfaction was related to reported side-effects, with those reporting side-effects experiencing lower satisfaction with medication than those without reported side-effects. CONCLUSIONS: The results from this analysis suggest that PRO survey data collected through a random sample of members of the on-line patient community iGuard.org can be representative of the spectrum of anticipated treatment satisfaction responses. Continuing to explore the potential of direct data capture from on-line patients will be important as researchers seek faster and cheaper alternatives to traditional physician-based recruitment.