(1) Background: Outpatient parenteral antibiotic therapy (OPAT) is a well-established and cost-effective measure that improves the efficient use of healthcare resources and increases bed availability. Only limited published data is available to illustrate OPAT implementation and outcomes in Saudi Arabia. The main objective of this study was to evaluate the effectiveness of OPAT in a tertiary center in Saudi Arabia. (2) Methods: In this retrospective study, clinical charts of enrolled patients were reviewed in a tertiary care center from the initial month of November 2017 to March 2020. All admitted patients with a central line and who enrolled in the OPAT of the hospital during this study period were included. The primary outcome was the 30-days readmission rate of OPAT patients. Secondary outcomes were factors associated with OPAT failure. Descriptive analysis of the data was used to express the results. (3) Results: We enrolled 90 patients; 54 (60%) were male; the mean age was 55.16 (±17.7) years old. The mean duration of the antimicrobial treatment was 21.9 (+24.6) days. All patients completed the intended course of therapy. Ertapenem was the most frequently used antimicrobial (43%), followed by vancomycin (11.2%). Urinary tract infections (UTIs) are some of the most common bacterial infections in 25 patients (26.9%), followed by osteomyelitis in 16 patients (17.2%). Extended-spectrum beta-lactamase E.coli was the highest common isolated microorganism (44.9%), followed by methicillin-resistant Staphylococcus aureus MRSA (16.9%). The readmission to the hospital during therapy was required for 12 patients (13.3%). Shifting from hospital care to OPAT care resulted in cost savings of 18 million SAR in the overall assessment period and avoided a total of 1984 patient days of hospitalization. (4) Conclusion: The findings have shown that OPAT therapy was effective with minimum hospital readmissions and therapy complications. OPAT programs can reduce healthcare costs and should be integrated into practice