Background: Direct oral anticoagulants (DOACs) share many indications with warfarin but require less frequent follow-up and monitoring. There is limited data available on the prescribing of DOACs and appropriate laboratory monitoring in a real-world clinical setting. Objective: To determine if patients receiving care at 2 University of Florida (UF) Health Internal Medicine clinics are prescribed DOACs according to Food and Drug Administration (FDA)–approved labeling. Secondary objectives were to determine the percentage of patients receiving appropriate baseline laboratory tests prior to DOAC initiation and the frequency of laboratory monitoring. Methods: This retrospective chart review evaluated patients enrolled at 2 UF Health Internal Medicine practices within the UF Health system who were prescribed a DOAC between April 2014 and April 2015. Adherence to FDA-approved dosing recommendations and baseline laboratory tests were compared to previously published data. This study was approved by the UF Institutional Review Board. Results: A total of 194 patients met inclusion criteria. Ninety-six patients (49.5%) were on a DOAC prior to data collection; 98 patients (50.5%) started a DOAC during data collection. Of the 194 patients, 155 (79.9%) were prescribed DOACs per FDA-approved labeling (P = .0005); 79 (40.8%) obtained a complete blood count, serum creatinine, and liver function tests prior to DOAC initiation. Conclusions: Prescribing practices were significantly better than published data; however, 1 in 5 patients were not prescribed a DOAC according to FDA-approved labeling. Less than half of the patients started on a DOAC obtained the recommended labs prior to medication initiation.