Background: Carbapenem-resistant Enterobacteriaceae (CRE) prevalence has been increasing in Saudi Arabia, posing a significant public health concern. Antimicrobial stewardship programs (ASPs) play an important role in reducing resistance by ensuring appropriate antibiotic use. Our study aimed to assess the appropriateness of meropenem prescriptions pre-ASP and post-ASP implementation in the Intensive Care Unit (ICU) ward. Method: This is a retrospective quasi-experimental pre–post study conducted over 3 years, from 2020 to 2023 at King Abdullah bin Abdulaziz University Hospital (KAAUH). The study included adult ICU patients who received meropenem therapy. The primary objective was to evaluate the appropriateness of meropenem prescriptions in the ICU before and after ASP implementation. The secondary objectives were to identify reasons for inappropriate prescribing and evaluate the interventions implemented to address inappropriate meropenem use. Result: A total of 113 patients were included: 34 in 2020, 41 in 2022, and 38 in 2023. Appropriate meropenem prescribing increased significantly from 23.5% in 2020 to 26.8% in 2022 and 57.9% in 2023 (p = 0.003), while inappropriate prescribing decreased from 76.5% to 73.2% and 42.1%, respectively. Treatment duration also differed significantly across study periods (p = 0.002), with courses of 7–10 days increasing from 24.2% in 2020 to 53.7% in 2022 and 52.6% in 2023, while courses exceeding 10 days decreased from 51.5% to 12.2% and 18.4%, respectively. Among inappropriate prescriptions, an inappropriate antimicrobial spectrum was the predominant reason (81.9%), with no inappropriate dosing identified. Documented stewardship interventions differed significantly across periods (p < 0.001): de-escalation increased from 0% in 2020 to 43.3% in 2022 and 50.0% in 2023, while prescriptions completed without documented intervention decreased from 69.2% to 23.3% and 18.8%, respectively. Conclusion: ASP implementation was associated with a significant improvement in the appropriateness of meropenem prescribing and a shift toward shorter treatment durations among adult ICU patients. Nevertheless, inappropriate prescribing remained substantial in the second post-implementation year, emphasizing the need for continued antimicrobial stewardship interventions and ongoing monitoring of carbapenem use.