Coronary artery disease is a leading cause of morbidity and mortality worldwide. Its management involves a combination of lifestyle modifications and medical interventions. However, the effectiveness of treatments is highly dependent on patient adherence to the prescribed treatment regimen. To explore the adherence level of patients with coronary heart disease to treatment regimen, identify factors affecting adherence, determine health-related quality of life, and measure the relationship between adherence of coronary heart disease patients to treatment regimen and health-related quality of life. Cross-sectional study was conducted in outpatient cardiology clinics of three private hospitals in Jeddah City including 222 coronary patients under treatment. An interview format, pre-coded, pilot tested was used. Arabic version of the RAND 36-item health survey was used. 43.2% of patients followed multiple treatment plans (p=0.000). 73.9% of patients insignificantly had comorbid conditions. Factors that significantly affected adherence to the treatment plan were availability of medications (p=0.02), side effects of medications (p=0.001), patient-physician relationship (p=0.002), development of complication (p=0.001), follow-up schedule (p=0.000), continuous health education (p=0.000). There was a significant difference between non-adherent and adherent groups for all scales of the RAND 36-item health survey. The significant predictors include work status, the treatment plan, and associated comorbid conditions. More than half of CAD patients were non-adherent to their treatment regimen. Factors affecting adherence level include availability, side effects, development of complications, cost of medications, and patient-physician relationship.