Objectives: This study aimed to evaluate discharge against medical advice (DAMA) in percutaneous coronary intervention (PCI) and how DAMA affects readmissions. Background: DAMA is infrequent but associated with poor patient outcomes. DAMA in the context of PCI has not been described in the published reports. Methods: The authors analyzed patients in the Nationwide Readmission Database between 2010 and 2014 with a PCI procedure who were either discharged home or against medical advice. The primary endpoint was all-cause 30-day readmissions and their causes. Descriptive statistics were used to compare DAMA with patients discharged home, and multiple logistic regressions were used to determine patient characteristics associated with DAMA and readmission. Results: Among the 2,021,104 patients in the analysis, the proportion of patients who DAMA was 0.5% (n = 10,049). The 30-day readmission rate for patients who were DAMA and those discharged home was 16.8% and 8.5%, respectively (p < 0.001). Important predictors of DAMA included diagnosis of acute myocardial infarction (odds ratio [OR]: 1.37; 95% confidence interval [CI]: 1.25 to 1.51; p < 0.001), smoking (OR: 1.71; 95% CI: 1.57 to 1.86; p < 0.001), drug abuse (OR: 1.82; 95% CI: 1.60 to 2.06; p < 0.001), and alcohol misuse (OR: 1.53; 95% CI: 1.32 to 1.78; p < 0.001). DAMA was the strongest predictor for readmission (OR: 1.89; 95% CI: 1.71 to 2.08; p < 0.001). DAMA patients were more likely to have neuropsychiatric reasons for noncardiac causes of readmission (8.3% vs. 2.4%) and acute myocardial infarction for cardiac causes of readmission (39.4% vs. 19.5%) compared with patients discharged home. Conclusions: DAMA occurs in approximately 0.5% of patients following PCI and is strongly associated with readmission within 30 days. Interventions should be developed to reduce DAMA in high-risk groups and initiate interventions to avoid complications and readmission when it occurs.