It is the standard practice in antidepressant efficacy trials (AETs) to exclude potential participants with major depressive disorder (MDD) who score below a threshold on the Hamilton Rating Scale for Depression (HAM-D). It is unknown to what extent various cutoff scores impact on the generalizability of these trials. In the present report, we sought to determine how many patients with MDD presenting to an outpatient practice would fail to qualify for an AET because their symptoms were not sufficiently severe, and to what extent the variability in HAM-D cutoff scores impacts exclusion rates. Fifteen hundred individuals presenting for an intake at a psychiatric outpatient practice underwent an evaluation with semistructured diagnostic interviews. Five hundred and three patients received a principal diagnosis of nonbipolar, nonpsychotic MDD. Thirty-nine AETs published in five leading journals during the past 7 years were reviewed, 36 of which required a minimum score on the HAM-D for inclusion. We applied the HAM-D cutoffs used in these AETs to the 503 depressed patients to determine how many would qualify for each AET. Based on the least and most restrictive cutoff scores, between 11.3% and 71.0% of the depressed patients from our practice had an insufficient HAM-D score to qualify for an AET. The two most commonly used cutoff scores would lead to the exclusion of almost half of our sample. AETs tend to include the subset of depressed individuals with moderate to severe MDD and exclude a significant proportion of depressed patients who have mild MDD. The implications of these findings are discussed.