Background: Medication adherence after percutaneous coronary intervention (PCI) is essential to preventing the risk of restenosis. Even though Type D personality and depression have been known to affect medication non-adherence, their combined influence on PCI patients remains unclear. Aim: We aimed to identify how both Type D personality and depression were associated with medication non-adherence for 3 months after successful PCI. Methods: This prospective cohort study included 257 PCI patients, who took 3 or more cardiac medications, at a university hospital. We measured sociodemographic and clinical variables, Type D personality, depression, and medication non-adherence using face-to-face interviews and medical record reviews. Results: The total prevalence of medication non-adherence at the one- and three-month follow-ups was 14% and 16%, respectively. At one month, the prevalence of those with a combination of Type D personality and depression (23.4%) and depression alone (24%) was significantly higher than other groups. At three months, the prevalence of the Type D personality-only group (39.1%) was the highest. Type D personality increased the risk of medication non-adherence 5.089 times at three months, while depression increased it 2.6 times at one month. However, the risk of medication non-adherence was not increased in patients with combined Type D personality and depression. Conclusions: Individual assessments of Type D personality and depression are required. Therefore, psychological interventions focusing on personality and depression are crucial. Longitudinal follow-up studies must explore the interaction or individual impact of Type D personality and depression on medication non-adherence and other negative outcomes.