Recognizing the effects of acculturation on quality of life and emotional health, especially during pregnancy, we developed an intervention that would target these factors in order to improve maternal well-being during the prenatal period and potentially improve infant outcomes, particularly preterm birth for Mexican-American women (Latinas).The purpose of these pilot studies was to test the acceptability, feasibility, and preliminary efficacy of the mastery lifestyle intervention (MLI) to decrease depressive and anxiety symptoms and improve coping as implemented in prenatal clinics with culturally homogenous groups of Latinas.The MLI was tested in three small pilot studies (n = 15), one in El Paso, Texas (an urban area), and two in Bastrop, Texas (a rural area outside Austin), for acceptability and feasibility. A pretest/posttest, quasi-experimental design was used with pregnant self-identified Mexican-American Latinas at 14-20 weeks' gestation. Measures of anxiety, depressive symptoms, and positive and negative coping were used.Feasibility was a success in terms of implementation of the MLI in an active prenatal clinic setting and the use of electronic tablets for data collection and entry of data into REDcap. Satisfaction was high, with the location of the MLI being at their primary OB/GYN clinic. Participants reported that six intervention sessions appear to be ideal as was the class length of 1.5 to 2 hours. On Cohen's d, there were medium to large effect size decreases in depressive and anxiety symptoms and small to medium effect size decreases in the use of negative coping strategies and small effect sizes for increases in positive coping strategies.Pilot testing of the MLI indicated that it was well accepted from the participants and feasible as a culturally tailored behavioral therapy administered in a group setting by nurse practitioners. Our initial pilot results also suggest preliminary efficacy as indicated by moderate to large Cohen's d effect sizes for depression and anxiety.