Background: Uncertainty is inherent in medicine, and trainees are particularly exposed to the adverse effects of uncertainty. Previous work suggested that junior residents seek to leverage the support of supervisors to regulate the uncertainty encountered in clinical placements. However, a broader conceptual framework addressing uncertainty experience, from the sources of uncertainty to residents' responses, is still needed. Objective: To capture the spectrum of uncertainty experiences in medical residents, providing an integrative framework that considers the influence of specialties and training stages on their experience with clinical uncertainty. Design: We used Hillen's uncertainty tolerance framework to conduct a thematic template analysis of individual and focus group interviews, identifying themes and subthemes reflecting residents' experience of clinical uncertainty. Participants: Medical residents from diverse medical specialty training programs, across five French medical schools. Approach: Qualitative study driven by an interpretivist research paradigm. Results: Twenty residents from all years of medical residency and diverse medical specialties were interviewed during three focus groups and five individual interviews. They described managing treatments, making ethical decisions, and communicating uncertainty, as their major sources of uncertainty. We identified residents' delayed response to uncertainty as a key theme, fostering the development of experiential learnings. Prior clinical experience was a key determinant of uncertainty tolerance in medical residents. Entrusting residents with responsibilities in patient management promoted their perception of self-efficacy, although situations of loneliness resulted in stress and anxiety. Conclusion: Residents face significant uncertainty in managing treatments, ethical decisions, and communication due to limited clinical experience and growing responsibilities. Scaffolding their responsibilities and clearly defining their roles can improve their comfort with uncertainty. To that extent, effective supervision and debriefing are crucial for managing emotional impacts and fostering reflection to learn from their uncertain experiences.