Background: Coronary artery disease (CAD) remains a significant health burden globally, often necessitating invasive interventions, such as angioplasty and coronary artery bypass grafting (CABG), to alleviate symptoms and improve outcomes. Beyond clinical efficacy, understanding the impact of these procedures on the quality of life (QoL) and psychological well-being is crucial for comprehensive patient care. Methods: This cross-sectional study investigated QoL and psychological impact in CAD patients who underwent PCI or CABG in a semi-urban population in South India. Participants completed the World Health Organization Quality of Life Scale (WHOQOL-BREF) and Hamilton Depression Rating Scale (HDRS) to assess various QoL domains and depressive symptoms, respectively. Demographic and clinical data were also collected to contextualize the findings. Results: A total of 75 patients with CAD (40 PCI and 35 CABG) participated in this study. The PCI group demonstrated comparable QoL scores across physical health, psychological well-being, social relationships, and environmental factors compared with the CABG group. However, significant differences were observed in the overall QoL domain, favoring the angioplasty group (p = 0.049). Conversely, the CABG group exhibited higher mean HDRS scores and a greater prevalence of moderate-to-severe depressive symptoms compared to the angioplasty group. Conclusion: This study highlights the differential effects of angioplasty and CABG on QoL and psychological well-being in patients with CAD in semi urban South India. While PCI may offer advantages in immediate QoL outcomes, patients undergoing CABG may experience greater psychological distress post-procedure. These findings underscore the need for personalized patient care strategies and enhanced psychological support to optimize CAD management outcomes.