Background: NSABP P-2 (STAR) was a randomized, double-blinded trial of tamoxifen vs raloxifene for the reduction of breast cancer incidence. The initial report from 2006 found raloxifene to be as effective as tamoxifen in preventing invasive breast cancer, but with fewer associated toxicities. In 2010 updated results indicated that raloxifene retained 76% of the effectiveness of tamoxifen in preventing invasive breast cancer and remained less toxic. Methods: May 31, 2012, STAR was permanently closed to followup. This current and final update is based on data through the end of followup for invasive and noninvasive breast cancer, other cancers, vascular events, and deaths. The final analysis comprises the same 19,490 women (9736 in the tamoxifen group and 9754 in the raloxifene group) as the 2010 update report. The median time of followup as of May 31, 2012, was 9.7 yrs. Results: Similar to the previous update, raloxifene remains less effective in preventing invasive breast cancer than tamoxifen (RR = 1.19, 95% CI = 1.04–1.37). For noninvasive breast cancer, the borderline statistically significant difference between treatment groups seen in the original findings continues to decrease (RR = 1.09, 95% CI = 0.88–1.36). Raloxifene also continues to have a better profile than tamoxifen re thromboembolic events (RR = 0.80, 95% CI = 0.66–0.96) and uterine cancer (RR = 0.56, 95% CI = 0.40–0.79). There were no statistically significant differences between treatment groups for any other site of cancer. There was, however, a borderline statistically significant all-cause mortality difference between the treatment groups. The death rates per 1000 in the raloxifene and tamoxifen groups were 4.10 and 4.73, respectively (RR = 0.87, 95% CI = 0.75–1.00). Conclusions: Raloxifene has retained approximately 81% of the effectiveness of tamoxifen in preventing invasive breast cancer and continued to grow closer to tamoxifen in preventing noninvasive breast cancer. Raloxifene has also maintained a better profile with respect to uterine disease, thromboembolic events, and death. Support: U10CA37377, -69974; -180868 -180822; -189867; -44066; Elli Lilly and Company; AstraZeneca Clinical trial information: NCT00003906