Coronary artery disease (CAD) is often associated with the older generation. However, in recent years, there is an increasing trend in the prevalence of CAD among the younger population; this is known as premature CAD. Although biomarkers for CAD have been established, there are limited studies focusing on premature CAD especially among the Malay male population. Thus, the aim of this research was to compare the biomarkers between premature CAD (PCAD) and older CAD (OCAD) among Malay males. Subjects, recruited from the Universiti Kebangsaan Malaysia Medical Centre and National Heart Institution, were divided into four groups: healthy control < 45 years old; premature CAD (PCAD) < 45 years old; healthy control > 60 years old; and older CAD (OCAD) > 60 years old, with n = 30 for each group. Ten potential markers for CAD including soluble sVCAM-1, sICAM-1, interleukin-2, interleukin-6, interleukin-10, Apo-E and Apo-A1, homocysteine, CRP, and vitamin D levels were examined. Our results revealed premature CAD patients had significantly higher values (p < 0.05) of sVCAM-1, CRP, interleukin-6, and vitamin D when compared to the age-matched controls. Similarly, older CAD patients showed higher levels of sVCAM-1, CRP, and interleukin-2 when compared to their age-matched controls. After adjusting for multiple parameters, only CRP remained significant for PCAD and interleukin-2 remained significant for CAD. This indicates that premature CAD and older CAD patients showed different profiles of protein biomarkers. CRP has the potential to become a biomarker for premature CAD while interleukin-2 is a better biomarker for older CAD together with other typical panels of protein biomarkers.