Extending a consistent pharmacy antimicrobial stewardship weekend service was a newly implemented initiative. We sought to evaluate the impact of incorporating an Infectious Diseases (ID)-trained clinical pharmacist into an antimicrobial stewardship program (AMS) during weekends. The number of documented interventions was 451 on 362 patients compared to 115 interventions on 108 patients during the pre-implementation period (p = 0.04), with interventions primarily targeting Watch antibiotics, as classified by the WHO AWaRe classification. A reduction in the LOS was observed, with a median of 16 days (8-34) during the post-implementation period compared to 27.5 days (10-56) during the pre-implementation period (p = 0.001). The median DOT increased during the post-implementation period to 8 (6-11), versus the increase to 7 (4-11) during the pre-implementation period (p ≤ 0.001). Finally, there was no significant difference observed in healthcare-associated CDI and infection-related readmission. This is a retrospective single-center, pre-post quasi-experimental study. Data including the documented pharmacist interventions were collected from the electronic medical record (EMR), the pre-implementation phase was in 2020, and post-implementation was in 2021. The primary outcome was to identify the number of AMS interventions through prospective audit and feedback review analysis. Secondary outcomes included antibiotic days of therapy (DOT), length of hospital stay (LOS), healthcare-associated Clostridioides difficile infection (CDI), and infection-related readmission. The pharmacist-driven weekend AMS is an opportunity for pharmacists to intervene and optimize patients' care plans. This initiative demonstrated significant increased AMS-related interventions, promoted judicious antimicrobial use, and contributed to a reduced length of hospital stay. Our findings need to be replicated in a larger prospective study.