Warfarin is an important therapy for children with heart disease. We assessed the impact of a computerized warfarin-dosing software program on measured INR values using a historical case-control design. Children (infant to 20 years of age) with cardiac disease managed with warfarin between September 1, 2006, and August 31, 2009 were included in the analysis. Warfarin therapy was tailored to specific underlying conditions based on consensus guidelines. Before the use of dosing software, medication adjustments were made by physicians using published guidelines. After software implementation, dosing adjustments were based on the software algorithm. There were 86 subjects in this analysis, and the most common indication for warfarin was prosthetic valve. Overall, the incidence of adverse bleeding events was 1.3% per patient-year. An analysis of patient-related factors associated with a low percentage of time within goal range demonstrated that both female sex (P = 0.048) and nonwhite race (P = 0.037) were significantly associated with less time in the target range. Use of the software program was associated with an increase in the percentage of time during which the INR was within the target range from 41.4 to 53.1% (P < 0.001). Incorporation of a computerized software program to assist dosing can improve the percentage of time that children with cardiac disease requiring warfarin remain within the target therapeutic range. Strategies to improve management and decrease sex and racial disparities in this population are needed.