The study examines the optimum condition of an electro-coagulation (EC) unit for treatment of hospital wastewater (HWW) using iron (Fe) electrodes. The impact of factors such as pH, current, and electrolysis time on COD, chloride, and anode dissolution was investigated. For this purpose, Box-Behnken (BB) design based on the response surface methodology (RSM) was used to design and analyze the results. The predicted value of chemical oxygen demand (COD) and chloride removal at optimum conditions (pH: 7.41, current: 2.64 A and electrolysis time: 41.31 min) were 92.81% and 71.23%, respectively. At same optimum conditions, the value of energy and electrode consumption per kg of COD was 0.06376 kWh/ kg COD and 1.362 kg/kg COD, respectively. High value of R 2 (i.e., R 2 > 99%) for all three responses (Y 1 , Y 2 , and Y 3) obtained from ANOVA confirms that the proposed model is valid, accurate, and acceptable. The kinetic study shows linear relationship and follows pseudo-first-order kinetics. Pareto graph shows that the percentage impact of current factor on COD and chloride removal was maximum, that is, 54.984% and 66.79%, respectively. Lastly, the total cost of EC treatment was calculated in terms of COD removal and was found to be 55.47 ₹/kg COD. © 2020 Water Environment Federation • Practitioner points • Using Fe electrode results in 92.81% COD and 71.23% Chloride removal, respectively. • High value of R 2 > 99% for all three responses from ANOVA confirms the proposed model is valid. • Pareto analysis shows current factor has maximum percentage impact on pollutant removal. • Kinetic study shows linear relationship and follows pseudo-first-order kinetics.