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Introduction: So far, there is no evidence available to demonstrate the relationship between five subgroups of total cholesterol/high density lipoprotein cholesterol (TC/HDL-C) ratio with premature myocardial infarction (MI). Objective: We conducted a case control study to probe more features of the relation between TC/HDL-C ratio and the five subgroups of the ratio with myocardial infarction under 55 years and above it. Method: A hospital based case control study with incident cases was designed. Cases and controls were comprised of 523 under 55-year and 699 above 55-year documented newly diagnosed MI cases, respectively. Standardized clinical and para clinical method were used to ascertain disease and risk factors. Independent sample t-test, Pearson chi square test, Odds ratios and Mantel-Haenszel test and logistic regression analysis conducted to evaluate relationships. Results: This study enrolled 1222 MI cases. Patients with very low risk category of TC/HDL-C ratio estimated OR=0.18 with 95% confidence interval (CI) (0.04–0.72) for developing MI under 55 years. Patients who had low risk category of TC/HDL-C ratio having OR=0.26 95% CI (0.07–0.89). Low risk and very low risk categories of the TC/HDL-C ratio compare to high risk subgroup of the ratio demonstrate decreased risk of developing MI under 55 years p