Background: Research has shown that lack of treatment adherence is a serious problem, especially among patients with psychiatric disorders. The current study was conducted to assess adherence and patient preference among individuals taking Wellbutrin SR (bupropion) for depression, as well as their interest in a once-daily formulation of bupropion. Methods: A 20-item web-based survey was administered to 527 individuals (276 men and 251 women) recruited through an online panel. All participants were at least 18 years of age, diagnosed with major depressive disorder, and had been taking Wellbutrin SR for at least 6 weeks. Survey items addressed treatment regimen, adherence, satisfaction with Wellbutrin SR, and interest in a once-daily formulation of bupropion. Results: The majority of respondents reported taking Wellbutrin SR twice a day (67%). Only 15% of once-daily users were nonadherent compared to 37% of twice-daily users and 65% of thrice-daily users. The most common reason reported for missing a dose of Wellbutrin SR was simply forgetting to take it (49% of twice-daily users and 65% of thrice-daily users). Results indicated that 77% of twice-daily users and 94% of thrice-daily users were interested in a once-daily formula. Conclusions: A reduction in dosing frequency is favored by Wellbutrin SR users and likely to improve their adherence to treatment. Because greater adherence has been shown to facilitate symptom relief, improvements in quality of life, and reductions in healthcare expenses, the results of this study support the value of the recently released once-daily formulation, Wellbutrin XL.