Purpose: Proton pump inhibitors (PPIs) are prescribed for the treatment of gastric reflux disease, but such medications might also influence bone metabolism. Therefore, the primary goal of this study was to determine if bone loss severity at dental implants could be associated with PPI use. Materials and Methods: Dental, medical, and radiographic history records of patients receiving dental implants at the University at Buffalo, School of Dental Medicine from 2000 to 2017 were reviewed in this retrospective clinical study. Bone loss around each implant was evaluated radiographically by direct measurement of crestal bone loss and by counting the number of radiographically evident exposed threads. PPI use was confirmed by medical record examination. The effects of systemic factors were assessed. Confidence intervals (CI) and P values of mean differences between PPI and non- PPI groups were computed via IBM SPSS Statistics v.25. Results: A total of 1,480 implants from 635 patients were used in this study. Greater crestal implant bone loss was associated with patients with a history of PPI medication use. Mean crestal bone loss of 1.60 mm was noted at implants from PPI patients, in contrast to 1.01 mm of crestal implant bone loss at implants from the non-PPI group (group difference = 0.59 mm, 58.40% increase, P = .024, CI [95%] = 0.08 to 1.09 mm). Following adjustment for systemic factors, those effects persisted, with crestal implant bone loss of 1.87 mm from PPI patients, in contrast to 1.04 mm from non-PPI patients (group difference = 0.83 mm, 79.80% increase, P = .028, CI [95%] = 0.09 to 1.56 mm). Similarly, 0.63 exposed threads per implant were found in the PPI group, in contrast to 0.38 supracrestal implant threads in the non-PPI patient group (mean difference = 0.25 exposed threads, 65.8% increase, P = .039, CI [95%] = 0.01 to 0.50 mm). After excluding systemic factors, a similar pattern was observed with 0.79 vs 0.36 threads exposed from subjects taking PPIs, compared with those not taking PPIs, respectively (mean difference = 0.43 exposed threads, 119.4% increase, P = .014, CI [95%] = 0.09 to 0.77 mm). Conclusion: The data suggest that PPI medications are related to more loss of crestal bone at implant sites. Patients receiving implant therapy might require more frequent periodontal maintenance. Keywords: bone loss, dental implants, proton pump inhibitor