INTRODUCTION: Assessing the effectiveness of antibiotics and communicating the problem of resistance are essential when devising antimicrobial stewardship programs (ASPs) in hospital settings. The Drug Resistance Index (DRI) is a useful tool that combines antibiotic consumption and bacterial resistance into a single measure. In this study, we used the DRI to assess the impact of introducing a new antibiotic restriction form on antibiotic effectiveness for the treatment of Gram-negative infections in the intensive care unit (ICU). METHODS: This was an observational study to assess and evaluate the antibiotic susceptibility of Gram-negative bacteria and antibiotic prescribing rates for the antibiotics indicated for Gram-negative bacteria following the introduction of a new antibiotic restriction form. The study was conducted from 2015 to 2017 at King Abdulaziz Medical City, a tertiary care facility in Jeddah, Saudi Arabia. Changes in antibiotic effectiveness before and after the introduction of the form were evaluated by calculating the DRI for four of the most common Gram-negative pathogens and eight commonly used antibiotic classes. RESULTS: The overall DRI for the adult ICU was higher (59.45) in comparison to the hospital-wide DRI (47.96). A higher DRI was evident for carbapenems and antipseudomonal penicillins + beta-lactamase inhibitors. Acinetobacter baumannii had the highest DRI followed by Klebsiella pneumoniae in both the adult ICU and hospital-wide. After the implementation of antibiotic restriction in the adult ICU, the DRI for carbapenems was significantly lower in the post-intervention phase (from 31.61 to 26.05) (p = 0.031). CONCLUSION: The DRI is a useful tool for tracking the effectiveness of antibiotics over time. The results of our study are significant in the way that it highlights the importance of having an effective antibiotic stewardship program in healthcare settings and regular feedback of antibiotic consumption data to the stakeholders to keep the antibiotic prescriptions in check, thereby ensuring their sustained effectiveness.