ABSTRACT Background: The Hospital environment is a reservoir for nosocomial pathogens that are mostly multidrug resistant which could pose a major therapeutic challenge. The aim of this study was to assess surface and air bacterial profile of selected wards at Felege-Hiwot Referral Hospital (FHRH). Materials methods: A hospital based cross-sectional study was carried out from 15th February to 30th April 2017. A total of 356 surface and air samples were collected from selected wards using 5% sheep blood agar (Oxoid, UK) as per the standard protocol. The samples were processed following standard bacteriological procedures at FHRH microbiology laboratory unit. Pure isolates were tested against nationally recommended antibiotics using Kirby-Bauer disc diffusion methods and the susceptibility pattern was determined based on Clinical Laboratory Standards Institute (CLSI). Data were entered and analyzed using SPSS version 23 for Windows. Results: Of the total 356 samples processed, 274 were from surfaces and 82 were from air. Among the total processed samples, 141 (39.6%) showed bacterial growth. From these positive samples, a total of 190 bacteria isolates. Gram positive isolates were predominant at 81.6% (n= 155) while the gram negatives were at 18.4 % (n= 35). The highest isolates bacteria were Coagulase negative staphylococci (CoNs) at 44%, followed by S.aureus at 37.4%, and Klebsiella species at 11.6%. The antimicrobial susceptibility pattern of the isolates showed that the overall sensitivity for Norfloxacillin was at 76.7% and 79.8% for gram positive and negatives, respectively. With regard to multidrug resistance profile, about 75% of the identified isolates were resistant for two and more antimicrobial agents tested