Although P values and statistical significance testing have become entrenched in the practice of biomedical research, their usefulness and drawbacks should be reconsidered, particularly in observational epidemiology. The central role for the null hypothesis, assuming an infinite number of replications, and the dichotomization of results as positive or negative are argued to be detrimental to the proper design and evaluation of research. As an alternative, confidence intervals for estimated parameters convey some information about random variation without several of these limitations. Elimination of statistical significance testing as a decision rule would encourage those who present and evaluate research to more comprehensively consider the methodologic features that may yield inaccurate results and shift the focus from the potential influence of random error to a broader consideration of possible reasons for erroneous results.