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.