Background: Cardiovascular diseases (CVDs) are the leading cause of mortality worldwide, with Triple Vessel Disease (TVD) representing a severe form that poses significant treatment challenges. In Pakistan, the burden of CVDs is high, exacerbated by genetic and lifestyle factors. Objective: To evaluate and compare the clinical outcomes of Percutaneous Coronary Intervention (PCI) and Coronary Artery Bypass Grafting (CABG) in patients diagnosed with Triple Vessel Disease (TVD) in a Pakistani cohort. Methods: This prospective cohort study was conducted at Lady Reading Hospital, Peshawar, from January 1, 2020, to December 31, 2021. A total of 400 patients diagnosed with TVD based on angiographic findings were enrolled. Inclusion criteria included age above 18 years, clinical diagnosis of stable angina or non-ST elevation myocardial infarction, and consent to participate. Exclusion criteria were previous revascularization procedures, concomitant valvular or congenital heart disease, and life expectancy less than a year due to non-cardiac conditions. Patients were assigned to either PCI or CABG based on clinical decisions by their managing cardiologists, considering anatomical considerations, comorbid conditions, and patient preferences. Baseline demographic and clinical data, including age, gender, smoking status, presence of diabetes, hypertension, and previous myocardial infarction (MI), were collected through patient interviews and medical record reviews. Clinical outcomes were monitored for 12 months post-procedure. Primary outcome measures included mortality, myocardial infarction, repeat revascularization, and stroke within 12 months. Secondary outcomes were hospital readmission rates and quality of life scores, measured using a standardized 10-point scale. Statistical analyses were performed using SPSS version 25, with continuous variables expressed as means and standard deviations and categorical variables as percentages. The chi-square test or Fisher’s exact test was used for categorical outcomes, and the student’s t-test or Mann-Whitney U test for continuous outcomes, with a p-value of less than 0.05 considered statistically significant. Results: The mean age of the participants was 62.5 ± 7.8 years, with 62 ± 8 years in the PCI group and 63 ± 7 years in the CABG group (p=0.45). Gender distribution was similar, with 255 males and 145 females overall (p=0.55). Smoking status, diabetes, hypertension, and previous MI were comparably distributed between the groups. Mortality was 5% in the PCI group and 3% in the CABG group (p=0.31). Myocardial infarction occurred in 10% of PCI patients compared to 5% of CABG patients (p=0.05). Repeat revascularization was required in 15% of the PCI group versus 7% of the CABG group (p=0.01). Stroke incidence was 2% in the PCI group and 1% in the CABG group (p=0.45). Hospital readmission rates were 20% for PCI and 15% for CABG (p=0.10). Quality of life scores were higher in the CABG group (8.0 ± 1.1) compared to the PCI group (7.5 ± 1.2) (p=0.04). Conclusion: CABG may offer superior outcomes compared to PCI in managing TVD among Pakistani patients, particularly in reducing myocardial infarction rates and repeat revascularization. Despite the invasive nature of CABG, its long-term benefits suggest it should be considered preferentially for patients with complex coronary anatomies. Clinical decisions should, however, be tailored to individual patient factors and preferences.