Background: Tablet splitting is widely used to individualize dosing of metoprolol tartrate when low-dose formulations are unavailable. However, splitting may lead to variability in dose accuracy, which can be clinically relevant at low dose strengths. This study compared the accuracy and precision of manual tablet splitting versus automated 3D printing for producing low-dose metoprolol tartrate tablets in a hospital setting. Methods: Commercial 25 mg metoprolol tartrate tablets from two manufacturers were manually split at Mayo Clinic into 12.5 mg halves and 6.25 mg quarters following established procedures. CurifyLabs’ Compounding System, including the Pharma Printer and CuraBlend^®-based formulations, was used at two hospital pharmacy sites and a compounding pharmacy to produce 6.25 mg and 12.5 mg tablets via 3D printing. Mass variation and content uniformity were evaluated using USP criteria and validated HPLC methods. Results: Manually split tablets showed high variability, with 6.25 mg quarters ranging from 24.9% to 142.8% API content and 12.5 mg halves from one manufacturer averaging only 66.6%, indicating frequent underdosing. In contrast, 3D-printed tablets achieved mean API contents within 90–103%, standard deviations below 5%, and acceptance values under 15 across all sites and formulations. Conclusion: Manual tablet splitting may not reliably meet pharmacopeial expectations for dose accuracy and content uniformity at lower dose strengths. Automated 3D printing produced consistent low-dose tablets and may offer a validated alternative where available.