The effects of electrocoagulation on COD removal of Nam Phong swine slaughterhouse wastewater (Binh Thanh District, Ho Chi Minh City, Vietnam) were investigated in this paper. For this purpose, response surface methodology (RSM) was employed to investigate the effects of three operating conditions on COD removal by electrocoagulation (EC) with iron electrodes. A central composite design (CCD) was used to optimize the EC process and to evaluate the individual and interaction effects of current density, electrolysis time, and initial pH. The results, based on statistical analysis, showed that the quadratic models for COD removal efficiency were significant at very low probability value (<0.0001) and high coefficient of determination (R² = 0.9754). Optimal conditions for COD removal were established at 130 A/m² current density, 9.5 min electrolysis time, and initial pH 8.5, in which a removal of 97.3% was achieved. Operating costs and sludge production at the optimum operating conditions were also calculated for the treatment process.