The flipped classroom is proposed as an answer to challenges in higher education. However, studies that explore its influence on first-year student motivation are largely lacking. Using the self-determination theory, this study examines the influence of large-scale flipped lectures, here called ‘expert labs’, on first-year student motivation in the context of a health sciences course (n = 219 students). A mixed-method approach was used, including questionnaires and focus groups with students and tutors. Paper-and-pencil surveys included questionnaires based on the Basic Personal Needs Satisfaction and Frustration Scale to compare student motivation in both traditional lectures and expert labs. Focus groups explored student’s and teacher’s experiences in relation to strengths and points for improvement of the flipped classroom. Results suggest that a large-scale flipped setting offers a possibility to enhance the relatedness of first-year students through increased interaction and in-class group assignments. First-year students appreciate the flexibility of pre-lecture preparation and an increased understanding of content through active application and peer learning. Nonetheless, first-year students indicate a need for guidance in pre-lecture preparation, explicit expectation management, and possibly the addition of external incentives to be motivated. When designing a large-scale flipped course, the challenge remains to tailor a blended course to support first-year student motivation by, for example, combining teacher support, scaffolding, and an autonomy supporting environment.