Prior studies of upper gastrointestinal bleeding (UGIB) and acute myocardial infarction (AMI) are small, and long-term effects of UGIB on AMI have not been delineated. We investigated whether UGIB in patients diagnosed with coronary artery disease (CAD) increased their risk of subsequent AMI. This was a population-based, nested case-control study using Taiwan's National Health Insurance Research Database. After propensity-score matching for age, gender, comorbidities, CAD date, and follow-up duration, we identified 1,677 new-onset CAD patients with AMI (AMI[+]) between 2001 and 2006 as the case group and 10,062 new-onset CAD patients without (AMI[-]) as the control group. Conditional logistic regression was used to examine the association between UGIB and AMI. Compared with UGIB[-] patients, UGIB[+] patients had twice the risk for subsequent AMI (adjusted odds ratio [AOR] = 2.08; 95% confidence interval [CI], 1.72-2.50). In the subgroup analysis for gender and age, UGIB[+] women (AOR = 2.70; 95% CI, 2.03-3.57) and patients < 65 years old (AOR = 2.23; 95% CI, 1.56-3.18) had higher odds of an AMI. UGIB[+] AMI[+] patients used nonsignificantly less aspirin than did UGIB[-] AMI[+] patients (27.69% vs. 35.61%, respectively). UGIB increased the risk of subsequent AMI in CAD patients, especially in women and patients < 65. This suggests that physicians need to use earlier and more aggressive intervention to detect UGIB and prevent AMI in CAD patients.