Background: Deprescribing of proton pump inhibitors (PPIs) can be considered in situations where the drug may no longer be necessary; however, this requires a careful discussion between patients and healthcare providers, often general practitioners (GPs). The aim of our study was to explore how GPs discuss PPI deprescribing with patients and compare that to how older patients would like to discuss this decision. Methods: We conducted a qualitative study using semi-structured interviews with GPs (n = 11) and patients aged ≥65 years who were taking PPIs (n = 4). Analysis of interviews was based on systematic text condensation. Results: We identified four main themes: (1) Reasons PPI deprescribing comes up, (2) Considering PPI deprescribing, (3) Discussion topics, and (4) Incorporating patient preferences into PPI deprescribing decisions. We found that PPI deprescribing often comes up during consultations for other problems or due to concern about medication burden in general. GPs discussed topics related to symptom control, such as the possibility of rebound symptoms, the need to taper PPIs, and what to do if symptoms returned. This aligned with what patients felt was important to discuss. Some GPs routinely incorporated patient preferences into decisions, whereas others did not. Conclusion: When discussing PPI deprescribing, the GPs in our study generally focused on topics related to symptom control. There was variability in how and if patient preferences were discussed. Greater focus may be needed on developing mechanisms to elicit and incorporate patient preferences into PPI deprescribing decisions. Future research could also explore more systematic approaches to reassess ongoing PPI use in an effort to curb unnecessary long-term use of PPIs.