Background: Multidrug-resistant Escherichia coli and Staphylococcus aureus are frequent culprits of severe healthcare-associated infections and have been identified as significant pollutants in hospital settings. The research into plasmids as potential carriers for transferring new resistance genes among clinical pathogens has been quite constrained. This study was conducted to determine the extent of multidrug resistance and the presence of plasmids in E. coli and S. aureus isolates derived from wastewater effluents at healthcare institutions in Lafia, Nigeria. Methods: A total of 231 effluent samples were collected from different units within the healthcare facilities and bacterial identification performed using standard CLSI identification techniques. Phenotypic multidrug resistance was analyzed using the Kirby-Bauer disc diffusion method while plasmid DNA was extracted by alkaline lysis and separated using 0.8% agarose gel electrophoresis. Results: A total of 167 (72.3%) and 175 (75.6%) samples were positive for E. coli and S. aureus, respectively. Both E. coli and S. aureus exhibited the greatest resistance to amoxicillin, with resistance rates of 79.0% and 66.3%, respectively. Conversely, the lowest resistance was observed for levofloxacin (26.3%) and cotrimoxazole (25.1%) in E. coli and S. aureus, respectively. The study did not find any significant correlation between the phenotypic antibiotic resistance profiles of the isolates and different wastewater discharge points (P>0.05). Out of the total isolates, 77 (46.1%) of E. coli and 51 (29.1%) of S. aureus were resistant to all tested antibiotics. A majority of these isolates exhibited multiple antibiotic resistance index (MARI) values greater than 0.5, with 87.4% of E. coli and 80.6% of S. aureus demonstrating multidrug resistance. Plasmid analysis for E. coli indicated that the largest proportion of the selected isolates (46.7%) carried double plasmids with sizes ranging from 1500 to 6000 base pairs (bp), and 6.7% had no plasmids. In the case of S. aureus, 53.3% of the isolates harbored a single plasmid with a size of 7500 bp, while 46.7% had no plasmids. Conclusion: The wastewater discharged from healthcare facilities in the examined community was found to be significantly contaminated with multidrug-resistant organisms carrying plasmids with resistance genes.