Clinically significant change refers to meaningful change in individual patient functioning during psychotherapy. Following the operational definition of clinically significant change offered by Jacobson, Follette, and Revenstorf (1984), several alternatives have been proposed because they were thought to be either more accurate or more sensitive to detecting meaningful change. In this study, we compared five methods using a sample of 386 outpatients who underwent treatment in routine clinical practice. Differences were found between methods, suggesting that the statistical method used to calculate clinical significance has an effect on estimates of meaningful change. The Jacobson method (Jacobson & Truax, 1991) provided a moderate estimate of treatment effects and was recommended for use in outcome studies and research on clinically significant change, but future research is needed to validate this statistical method.