Background: A maternal tetanus-diphtheria-and-acellular-pertussis (Tdap) vaccine is offered to all preg-nant women in the Netherlands in their second trimester since December 2019. However, former studies solely investigated the socio-psychological factors that influence vaccine acceptance among pregnant women in the third trimester. We identified predicting factors for attitude, intention and acceptance of maternal Tdap vaccination during the second trimester of pregnancy.Methods: As part of a large prospective cohort study, women early in pregnancy completed a question-naire on determinants regarding acceptance of maternal Tdap vaccination between 20 and 24w of gesta-tion. The vaccine was offered after completion of the questionnaire. A random forest model and Receiver Operating Characteristics (ROC) analyses were carried out to identify the factors most predictive for vac-cine acceptance on the whole data set, and also in sensitivity analysis on a subset reflecting the annual nationwide 70% vaccination uptake.Results: Among 1158 participants who were offered a Tdap vaccination between 20 and 24w of gestation, 1098 (94.8%) accepted and 60 (5.2%) rejected the vaccine. Random forest analyses identified intention as most predictive for acceptance, followed by attitude towards vaccination, beliefs regarding safety, risk perception of severity of side effects, moral responsibility, beliefs regarding effectiveness and risk percep-tion of susceptibility of side effects, with a sensitivity of 100% and a specificity of 40%, for which this com-bination could be improved by the ROC analysis to 82% and 67%, respectively. The sensitivity analysis yielded an order of predictors that generally corresponded with the initial model. Conclusions: Intention, attitude, beliefs on safety and effectiveness, risk perception of side effects and moral responsibility were most predictive for maternal Tdap vaccine acceptance during the second trime-ster of pregnancy, in accordance with studies regarding third trimester vaccination. These should be dis-cussed by healthcare professionals early in pregnancy to provide an informed choice towards vaccine acceptance.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/).