The objective of this paper was to identify the factors associated with moderate to high nicotine dependence in a sample of pregnant smokers from Romania. Data was collected through an ongoing cross-sectional pilot study from 130 pregnant smokers. The questionnaire included five main sections: socio-demographic information, medical and reproductive history, alcohol and smoking behaviors, emotional health and information regarding the relationship with the partner. Older age, first pregnancy, a negative screening for anxiety and depression, and negative partner interactions related to smoking were significantly correlated with increased odds of moderate to high nicotine dependence during pregnancy. In addition, high dyadic efficacy, low self-efficacy, high pregnancy-related anxiety, and a non-smoking life partner were correlated with increased odds of moderate to high nicotine dependence, although the results did not reach statistical significance. Once the level nicotine dependence is established, cessation treatment should target specific risks that are associated with this dependence. Maternal risk factors, spousal smoking status, and interactions in the couple hold promise in future tobacco cessation interventions. Future research should focus on both the prenatal smoking cessation and on postnatal relapse prevention among highly dependent women.