we never will know whether similarity exists for the unknown prognostic factors, we are reassured when the known prognostic factors are nicely balanced. Randomization doesn't always produce groups balanced for known prognostic factors. When the groups are small, chance may place those with apparently better prognoses in one group. As sample size increases, this is less and less likely (this is analogous to multiple coin flips: one wouldn't be too surprised to see seven heads out of ten coin flips, but one would be very surprised to see seventy heads out of one hundred coin flips). The issue here is not whether there are statistically significant differences in known prognostic factors between treatment groups (in a randomized trial one knows in advance that any differences that did occur happened by chance) but rather the magnitude of these differences. If they are large, the validity of the study may be compromised. The stronger the relationship between the prognostic factors and outcome, and the smaller the trial, the more the differences between groups will weaken the strength of any inference about efficacy. All is not lost if the treatment groups are not similar at baseline. Statistical techniques permit adjustment of the study result for baseline differences. Accordingly, readers should look for documentation of similarity for relevant baseline characteristics, and if substantial differences exist should note whether the investigators conducted an analysis that adjusted for those differences. When both unadjusted and adjusted analyses reach the same conclusion, readers justifiably gain confidence in the