OBJECTIVE: Clinical staff often help clinicians review and respond to messages from patients. This study aimed to characterize primary care staff members' experiences with inbox work. MATERIALS AND METHODS: In this qualitative study, we conducted direct observations and focus groups with clinical staff at 4 academic primary care clinics. We used inductive thematic analysis to code the resulting notes and transcripts for themes in staff members' experience with inbox work. RESULTS: Nine medical assistants and 3 nurses participated in the study. Staff described inbox work as fragmented, feeling like an assembly line, requiring frequent communication with other team members to clarify and manage tasks, and requiring navigation of expectations that varied between patients, clinicians, and clinics. Staff described some messages as being more difficult to manage due to how requests were posed, challenges with subsequent communication, and mismatches between data from different sources. Staff also described how tools that structured or automated message management aided inbox work. DISCUSSION: Staff addressed routine messages by following known protocols and appreciated tools that structured their inbox work. However, staff also regularly encountered messages with information that conflicted with clinic records or that contained multiple, redundant, or vague requests. Addressing these messages required additional work to clarify information (ie, data work) and manage resulting tasks (ie, articulation work). CONCLUSION: Clinic workflows and health information technology should support not only the readily standardized work of addressing routine messages but also the more varied work of preparing messages to be addressed in the first place.