Background: Antimicrobial resistance (AMR) is a major threat in pediatric intensive care units (PICUs). Data on resistance patterns in non-neonatal pediatric cohorts in Ethiopia remain scarce. This study assessed Bacterial Isolates and Predictors of High-Risk Antimicrobial Resistance Among PICU at Asella Teaching and Referral Hospital. Methods: A five-year (2020–2025) hospital-based cross-sectional study was conducted among patients aged 29 days to 14 years. Data were extracted from records using a structured checklist. Independent predictors of high-risk AMR were identified via multivariable logistic regression (p<0.05). Results: Among 217 participants, 52.5% had positive microbial growth. Gram-negative bacteria accounted for 54.5% of isolates, slightly predominating over Gram-positive organisms. Among 66 isolates, high-risk AMR prevalence was 68.2%, including extended-spectrum beta-lactamase (ESBL) (19.7%) and extensively drug-resistant (XDR) (15.2%) strains. Multivariable analysis identified length of PICU stay (AOR 7.59, 95% CI: 1.10–52.60; p=0.040) and adverse outcome at discharge (AOR 8.22, 95% CI: 1.39–48.63; p=0.020) as independent predictors. Invasive device duration and Gram-negative status were significant only in bivariate models. Conclusion: High-risk AMR (68.2%) is independently associated with prolonged hospitalization and adverse outcomes. These findings necessitate strengthened infection control, enhanced microbiological surveillance, and robust antimicrobial stewardship to mitigate multidrug-resistant pathogens in high-acuity settings.