Objective To assess the correlation between the insulin-based and C-peptide based HOMA-IR in the general population without diabetes in sub-Saharan Africa as well as to identify factors associated with IR. Results This was a cross-sectional study in urban settings in Yaoundé, Cameroon. We included 84 people with a body mass index (BMI) ≥ 18.5 Kg/m² and without diabetes (females: 72.6%; mean age: 37 years). IR was assessed using the following formulae: HOMA-IRINS = fasting insulin (mU/ml) x fasting plasma glucose (FPG) (mmol/L)/ 22.5; HOMA-IRCP1 = fasting C-peptide (mU/ml) x FPG (mmol/L)/ 22.5; and HOMA-IRCP2 = 1.5 + (FPG (mg/dl) x fasting C-peptide (ng/ml))/ 2800. Correlation (rho) between HOMA-IRINS and C-peptide based HOMA-IR was investigated using the Spearman rank test. The median (25th -75th percentiles) HOMA-IRINS, HOMA-IRCP1, and HOMA-IRCP2 were: 1.94 (1.36–3.50), 0.18 (0.11–0.27) and 9.91 (6.81–14.52), respectively. There was no correlation between the insulin-based and C-peptide-based HOMA-IR indices: rho = 0.043, p = 0.697. IR (HOMA-IRINS ≥ 2.8) was associated with obesity: A BMI ≥ 30 Kg/m² (adjusted odds ratio (aOR): 16.9, 95% confidence intervals (CI): 3.1–92.5) and being a student (aOR: 8.9, 95%CI: 2.1–38.2) were associated with IR.