Background: Interprofessional teams contribute to patient safety during clinical care. However, little is known about how interprofessional teams manage and cope with critical incidents in the emergency department (ED). Therefore, the study aimed to describe healthcare professionals (HCPs) perceptions of critical incidents linked to the enablers of and barriers to interprofessional teamwork in a high-risk setting, the ED. Methods: Individual interviews with HCPs regarding events at the ED were held during the period of May 2019–January 2020. The Critical Incident Technique approach was used to guide the interviews and the qualitative analysis. Data were analyzed inductively using qualitative content analysis. Results: Interview participants (n = 28) included 7 physicians (25%), 12 registered nurses (43%), 7 nurse assistants (25%) and 2 administrators (7%). Overall, 108 critical incidents were described. Eight categories that described functional and dysfunctional experiences within interprofessional teamwork were identified: salience of reflection; professional experience makes a difference; demanding physical and psychosocial work environment; balancing communication demands; lacking management support, structure, and planning; tensions between professional role and responsibility; different views on interprofessional teamwork; and confidence in interprofessional team members. Conclusion: Findings of this study indicate that poor ED-specific communication and limited professional experience are essential factors in handling critical incidents related to interprofessional teamwork. An important aspect of critical incident management is the ergonomics of the physical work environment and how it enables interprofessional teamwork. This study emphasizes the factors enabling interprofessional teamwork to manage critical incidents in the complex working environment of the ED.