Student persistence and retention are critical concerns for colleges. Although much research has been focused on first-generation college students and how their pre-college circumstances contribute to their failure to persist to a degree, little research has been done to focus specifically on first-generation students and how failure in gateway courses in the first year is related to persistence to a degree. This study examined how the type of gateway course failed (STEM or non-STEM), the number of gateway courses taken and failed, and the instructional modality for gateway courses that were taken and failed in the first year at a university related to failure to persist to a degree for first-generation college students. The study was based on rigorous quantitative analysis of ex post facto data related to 524 first-generation college students who were admitted to a small Texas public university and enrolled in a gateway course in their first year. The results of this study showed failure in gateway courses for first-generation college students had a significant relationship to failure to persist to a degree. This was found at the individual class level, in the total number of classes failed, and with regard to course modality. The findings of this study have implications for how universities assist first-generation college students in their pursuit of a college degree as well as implications for the types of classes and course modality that first-generation students should enroll in during their first year at the university. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://www.proquest.com/en-US/products/dissertations/individuals.shtml.]