Introduction: Infections with drug-resistant organisms (DRO) have been associated with poor patient outcomes. To tackle this global problem, it is necessary to understand the risk factors that predispose to infections with DRO. Methodology: This was a prospective observational study conducted over a three-year period at a tertiary-care hospital. Bacterial culture isolates from patients admitted in medicine wards with community or hospital-acquired infections were included. Logistic regression analysis was used to determine risk factors for drug-resistant infections. Results: Of the 295 patients with 323 isolates included, 40 (12.3%) had non-MDR (N-MDR) infections, 86 (26.6 %) had MDR infections and 197 (61%) had possible extensively drug-resistant (P-XDR) infections. History of previous admission in the preceding three months (Odds Ratio, OR = 4.53, 95% Confidence interval, CI = 1.8-11.42, p = -0.01), high SOFA score at admission (OR = 1.14, 95% CI = 1.0-1.290, p = -0.039) and prolonged duration of ventilation (OR = 1.25, 95% CI = 1.05-1.41, p = -0.012) were independently associated P-XDR infections when compared to patients with N-MDR. Conclusions: High rate of multidrug-resistant infections in the studied area is alarming. In this single-centre study, we elicited various risk factors for drug-resistant bacterial infections ranging from patient characteristics to iatrogenic risk factors during the hospital stay. Infections with P-XDR and MDR isolates independently increased hospital and ICU stay duration and were associated with increased mortality.