Healthcare waste management in Ethiopia has been a neglected activity by health service providers and lacked the attention it deserves. This study aimed to evaluate treatment efficiency of a constructed wetland system for the treatment of wastewater from Tikur Anbessa Specialized Referral Hospital. The raw wastewater was characterized by extremely high organic matter, nutrient load and high concentration of pathogenic microorganisms and low concentration of heavy metals. Four parallel aligned horizontal subsurface flow constructed wetland cells planted with Typha latifoila, Phragmites karka, mix of Typha latifoila with Phragmites karka, and un-vegetated control were used and the experiment was conducted within 12 weeks of operation. The treatment efficiency for each cells were assessed using the following water quality parameters: BOD, COD, TSS, NO3-, NH4+, PO43-, TP, S2-, SO42- , Heavy metals, total and fecal coliform and antibiotic resistant E. coli. The constructed wetland cell planted with mix of T. latifoila and P. karka showed highest removal efficiency for NH4+ (87.68%), PO43 (87.9 %), TP (87.7%), S2- (85.3%), SO42- (76.4%) and BOD (89.9%). Removal efficiency for COD ranged between 88.4 and 89.6% in all the vegetated cells. Highest removal efficiency for Cu was observed in the cell planted with mix of T. latifoila and P. karka. The constructed wetland planted with P. karka showed highest removal efficiency for Pb (86.6%) and Fe (81.1%), while the removal for Zn was higher in cells planted with T. latifoila and mix of T. latifoila and P. karka (98.9%). Equivalent removal efficiency for TSS (96.3%), TC (99 %) and FC (99%) was observed in both vegetated and un-vegetated constructed wetland cells. Resistant E. coli isolates were prevalent in all the influent and the effluent wastewater. In the influent wastewater, 100% resistance was observed against Gentamicin and Neomycin. Overall, the cell with a mix of T. latifoila and P. karka was found to be the most efficient cell exhibiting the highest removal of most of the pollutants in the influent hospital wastewater. This implies that the use of a combination of macrophytes can be potential candidate for large scale hospital wastewater treatment. The constructed wetland showed better removal for organic matter, nutrients and heavy metals. Further investigation was recommended for removal efficiency evaluation of constructed wetland for coliforms and antibiotic resistant bacteria. Keywords/ phrases: Antibiotic resistant E .coli, Constructed wetland, Hospital wastewater, Macrophytes, Tikur Anbessa Hospital, Wastewater treatment