BACKGROUND: Low density lipoprotein cholesterol (LDL-C) levels are used to estimate cardiovascular disease (CVD) risk and to guide prescriptions. To circumvent the challenges of direct LDL-C measurement, guidelines recommend the use of Friedewald formula derived LDL-C levels. Despite reported limitations of this formula, its validity in sub-Saharan Africans has not been adequately investigated. OBJECTIVE: To assess the validity of the Friedewald formula derived against directly (homogeneous) measured LDL-C in adult Cameroonians. METHODS: We reviewed the fasting lipid profiles of 2500 patients, performed between March 2012 and January 2016 using enzymatic colorimetric method (reference), at the Douala General Hospital laboratory. The Friedewald formula was used to calculate LDL-C from total cholesterol, high density lipoprotein cholesterol and triglyceride levels. Calculated LDL-C values were compared to the reference values, and clinical significance of differences between the two methods was assessed using total error allowable (TEa). RESULTS: The difference between means of calculated and the reference LDL-C values was neither statistically nor clinically significant (3.33±1.51 vs. 3.33±1.25mmol/l; p=0.704). The calculated LDL-C correlated positively with the measured LDL-C value (r=0.749) and both methods showed a good agreement on Bland-Altman plot. Conversely, there was only moderate agreement (kappa=0.478, 95% CI: 0.455-0.502) between the two values in the stratification of cardiovascular risk according to the National Cholesterol Education Program/Adult Treatment Panel III. Consequently, 40.6% of the participants were misclassified. CONCLUSION: Friedewald formula is technically accurate but has a modest clinical accuracy which can translate into a substantial misclassification of patients' cardiovascular risk and subsequent inappropriate therapeutic decisions.