BACKGROUND: Pregnant women have historically been excluded from participation in medication trials, in part due to the perceived risks of drug exposure to mothers and fetuses. However, little is known about pregnant women's attitudes toward risk and participation in such trials. AIMS: To address this knowledge gap and to identify factors that influence trial participation. MATERIALS AND METHODS: Australian women over the age of 18, currently pregnant or within six months of delivery, were recruited to participate in an online survey (n = 623) and follow-up interviews (n = 11). The survey investigated willingness to participate in five hypothetical drug trial scenarios of varying risk. Demographic and obstetric information, including COVID-19 vaccination status, was also collected. The impact of these factors on trial participation was analysed using ordinal regression. Interviews were subjected to thematic framework analysis using a priori and emergent themes. RESULTS: Nearly half of the respondents (48%) indicated a willingness to participate in at least one of the hypothetical trials. As trial risk increased participation likelihood decreased, especially if the risk was to the fetus, regardless of benefits to the mother. COVID-19 vaccination status and medication hesitancy were predictors of an unwillingness to participate. Three broad themes emerged from the qualitative data: risk-benefit analysis, quality of evidence, and trust. CONCLUSIONS: Overall, participants expressed a positive attitude toward research and medication trials during pregnancy, but were concerned about fetal risk. The findings of this study may help enhance trial design and the participation of pregnant women in medication trials.