Background: Antimicrobial resistance (AMR) has risen as a global health problem. In low-income countries, AMR individual testing is costly and often not done. Studies elsewhere, have shown that clinical wastewater is a single sample that represent a pool of so many individuals and comprise a cost effective screening endeavor that can improve empirical prescription (which is otherwise associated with exacerbation of AMR). This cross sectional study aimed at isolating and profiling AMR bacteria from hospital wastewater of Soroti regional referral hospital (SRRH). Methodology: In this cross section study, we prospectively collected samples of hospital wastewater over a period of one month from different hospital manholes. We cultured samples on different selective media and pure plated representative colonies depending on the colony characteristics. We then tested the isolates for antibiotic resistance using the Kirby-Bour disk diffusion method. We interpreted results according to CLSI 2020 using the diameters of zones of inhibition. We defined multidrug resistance as non-susceptibility to at least one agent in three or more antimicrobial categories. Results: Taken together, we isolated 35 bacteria from 22 samples collected from different manholes of the SRRH. Klebsiella spp were the majority (15/35; 43%). This was followed by Bacillus cereus (9/35: 26%), Escherichia coli (7/35; 20%), unidentified coliform 3 (3/35; 8%) and Pseudomonas (1/35; 3%). All isolates of Klebsiella spp were resistant to Ampicillin and Piperacillin/Tazobactum. Resistance to Cefotaxime and Ciprofloxacin was (12/15; 80%). However, Klebsiella was most susceptible to Gentamycin and Azithromycin (13/15; 86.7%). Susceptibility to Meropenem and Amikacin was (12/15; 80%). Other drugs that we tested for resistance against Klebsiella included Norfloxacin, Doxycycline, and Tetracycline (11/15; 26.7%), (9/15; 60%), (6/15; 42.9%) respectively. All isolates of E. coli were resistant to Cefotaxime, Ampicillin, Cefuroxime and Tetracycline. The isolates were most susceptible to Meropenem and Amikacin (1/7; 14.3%) and (2/7; 28.6%), respectively. They were highly resistant to Nalidixic Acid, Ciprofloxacin, Piperacillin/ Tazobactum and Levofloxacin (6/7; 85.7% for each drug). Other drugs that we tested for resistance included; Azithromycin, Norfloxacin and Doxycycline with resistance of (5/7; 71.4%) and Gentamycin with (4/7; 57.1%).