Objectives: This study aimed to assess  knowledge, medication adherence, and quality of life (QoL), as well as to identify associated factors and examine the relationships among these three outcomes in patients after percutaneous coronary intervention (PCI) at Hanoi Heart Hospital. Methods: A prospective longitudinal study was conducted among 120 patients who underwent successful first-time PCI at Hanoi Heart Hospital from May 2025 to January 2026. Data were collected before discharge and at 1 and 6 months after PCI. Knowledge was assessed using the CADE-Q-SV before discharge and at 6 months; medication adherence was assessed using the 8-item Morisky Medication Adherence Scale (MMAS-8), and QoL was assessed using the EQ-5D-5L at 1 and 6 months. Lifestyle behaviors were assessed at all three time points. Univariate and multivariable logistic regression analyses were performed to identify factors associated with knowledge, medication adherence, and QoL and to examine the relationships among these outcomes. Results: Among the 120 patients, 60.8% were aged ≥65 years and 69.2% were male. The proportion of patients with adequate knowledge increased from 58.3% before discharge to 63.3% at 6 months. Medication adherence decreased from 67.5% at 1 month to 62.5% at 6 months, whereas the proportion of patients with high QoL increased from 42.5% to 60.0%. Multivariable analyses showed that chest pain, affordability, exercise, and several psychological and care-related factors were associated with knowledge, medication adherence, or QoL at different follow-up time points (p<0.05). After adjustment, adequate knowledge was associated with medication adherence (aOR=4.2, 95% CI: 1.1–15.2; p=0.02). Medication adherence was independently associated with high QoL (aOR=8.4, 95% CI: 1.8–39.3; p=0.007), whereas knowledge was not significantly associated with QoL (aOR=0.5, 95% CI: 0.1–2.5; p=0.43). Conclusion: After 6 months of follow-up, the proportions of patients with adequate knowledge and high QoL increased, whereas medication adherence declined. Knowledge was associated with medication adherence, and medication adherence was independently associated with QoL. These findings highlight the need for continuous post-discharge care, with a focus on reinforcing knowledge, sustaining medication adherence, monitoring symptoms, and supporting health-promoting behaviors to improve long-term outcomes in patients after PCI.