The excess of events in the first year in the treated group was 1.4%, a relative hazard of 1.5, large enough that chance is an unlikely explanation (57 vs 38, 2P = .046). However, the nominal P value is hardly the issue, since the expectation was for a lesser, not an equal, number of events. The observational studies suggested as much as a 50% reduction, and the trial was designed to detect an intention-to-treat reduction of 24%. The design anticipated a 1-year delay in half the benefit, so that the expected result at the end of the first year can be construed to be a reduction in primary events of 12%. If this were the "true" value, a result as contrary as that observed would occur only once in 258 such trials. To produce the expected net benefit of 24% over the trial duration, the late event rate in the treated group would have had to be about 62% less than was observed. Over the entire trial, ignoring the earlier occurrence of events in the HRT group, the play of chance on a true relative risk reduction of 24% would produce at least the overall HERS result, on average, only once in 104 trials. Neither the first-year excess nor the overall HERS result can plausibly be dismissed as the play of chance on the expected effect.