The objective of the Genotype-Guided Dosing of Warfarin Therapy is to conduct a 1,965 participant randomized, double-blind trial comparing three possible approaches to guiding warfarin therapy initiation: 1) initiation of warfarin therapy based on an algorithm using clinical information and the individual's genotype relative to two genes known to influence warfarin metabolism (CYP2C9 and VKORC1 genes);2) initiation of warfarin therapy based on an algorithm using only clinical information;and 3) a standard guideline-based initiation strategy. The primary endpoint will be the difference in percentage of time participants spend within the therapeutic INR range (PTTR) during the first month of therapy. Secondary outcomes will be the PTTR during the first three months of therapy and other outcomes related to anticoagulation status, including: time to stable warfarin dosing defined as three consecutive INR measurements in the therapeutic range without a dose change and rate of INR above range (>4.0). Anticoagulation status outcomes will be analyzed at one, three and 12 months. Other secondary outcomes will include differences in rates, both at one, three months and 12 months of: major bleeds, combination of major and minor bleeds, combination of major bleeds and thromboembolic complications. Subgroup analysis by gender, ethnicity and age will be conducted to determine effects in women, various ethnic groups, and the elderly.