We read the article by Meduri et al1regarding the early use of low-dose steroids in ARDS with great interest. Although the results appear promising, detailed evaluation reveals a few concerning issues that may have resulted in an exaggeration of the treatment effect. First, the characteristics of the two groups were not balanced at baseline, with the control group having twice the incidence of catecholamine-dependent shock. Since shock has been directly associated with both length of mechanical ventilation and mortality,2this imbalance likely contributed to the differences in outcomes. Second, the technique of “periodic data inspection,” via unplanned interim analyses instead of a priori-defined evaluation points, allows a continuous look at the data with the ability to terminate the study early once a desired p value is met (which may not be significant at other times during the study). The authors fail to report key aspects of trial design, such as the planned sample size, the rules used in deciding to stop the trial, and adjusted estimates for interim analyses and early termination.3 Finally, although the authors report an intention-to-treat analysis, a significant percentage of control patients crossover and receive open-label methylprednisolone, effectively contaminating the control group and potentially obscuring the detection of any harm caused by steroids. Essentially, the study compares early vs delayed methylprednisolone treatment in patients with ARDS. With these limitations, the only reasonable conclusion that can be gleaned from this data is that the use of steroids in a small, unmatched cohort may have a beneficial effect on lung injury scores at day 7. Unfortunately, improvement in oxygenation and lung injury scores have not been found to correlate with clinical outcomes.4–5 Therefore, before incorporating methylprednisolone treatment into routine care of these patients, a larger, randomized, blinded, placebo-controlled study without crossover should be undertaken to better evaluate the effect of steroids in ARDS.