Depression occurring during pregnancy and postpartum (i.e., the perinatal period) is common and associated with adverse outcomes for women and their offspring. Mindfulness-based cognitive therapy (MBCT) has been shown to reduce risk for depressive relapse among at-risk individuals generally, and recent adaptations document the efficacy of MBCT among perinatal women specifically. In addition, MBCT, when delivered using a web-based format (Mindful Mood Balance [MMB] program), has demonstrated acceptability and feasibility for at-risk individuals generally. The aim of the present open trial study was to examine the feasibility, acceptability, and preliminary outcomes of MMB for use with pregnant women at risk for depressive relapse (N = 37). We predicted that MMB would be feasible and acceptable as assessed by session completion and participation in phone coaching calls, home practice completion, and self-reported satisfaction via questionnaire and interview. We also predicted that women would not demonstrate significant worsening of depression symptom severity during MMB, consistent with our focus on prevention. A brief case example based on a composite of participants is presented to illustrate the MMB structure and content and the phone coaching protocol. Participants demonstrated engagement with the program, reported perceiving benefits in the intended depression prevention targets of MMB, and sustained minimal to mild depressive symptom severity over the course of the program. Given these promising results and the potential benefits of averting depression for women and their families, further development and rigorous testing of MMB among at-risk pregnant women is warranted.