Background: Aspirin, when used with concurrent anticoagulation, increases the risk of gastrointestinal bleeding (GIB). Therefore, multisociety guidelines recommend prophylactic proton-pump inhibitors (PPIs) for patients receiving aspirin and anticoagulation. We aimed to determine rates and predictors of adherence to these recommendations. Methods: All adult inpatients discharged from the hospital on aspirin and anticoagulation from July 2009 to June 2014 were retrospectively evaluated for PPI prescription on discharge instructions. We used univariate and multivariate logistic regression to test for predictors of PPI prescription. Results: A total of 2422 patients were discharged on aspirin and anticoagulation; the mean age was 68 years and 53.2% were male; 42.2% were prescribed a PPI at discharge. On univariate analysis, factors associated with discharge PPI prescription included increased age (47.1% versus 37.9%), white race (47.3% versus 37.1-40.2%), higher aspirin dose (55.1% versus 39.4%), being married (46.2% versus 39.4%) and preadmission PPI use (96.6% versus 23.4%). On multivariate analysis, significant predictors of discharge PPI prescription were age 60-69 years [odds ratio (OR) 1.61] and 70-79 years (OR 1.48), and preadmission PPI use (OR 120.03). Lower odds of discharge PPI prescription included Medicaid (OR 0.55) or Medicare (OR 0.71) insurance, Spanish language (OR 0.63), and lower dose aspirin (81 mg) (OR 0.40). Conclusions: A total of 42.2% of patients discharged on aspirin and anticoagulation were prescribed PPIs. Older age and preadmission PPI use were predictive of PPI prescription, while Medicaid/Medicare insurance, Spanish language, and lower dose aspirin decreased the likelihood of discharge PPI prescription. This creates an opportunity to improve primary GIB prevention through quality improvement interventions.