Placebo response is thought to be a primary contributor to uninformative (failed) trials in clinical drug development. This study describes the development of a patient-reported assessment to detect likely placebo responders. A novel scale, the Placebo Response Screening Scale (PRSS), was developed to assess domains expected to be associated with placebo response. The scale was administered during the screening visit of a 4-week, placebo-controlled study of alprazolam and an investigational compound in 211 patients with generalized anxiety disorder (GAD). Items that predicted placebo response were identified. Sensitivity and specificity of the instrument were used to determine a threshold score for use in screening likely placebo response. The PRSS was then evaluated by comparing active treatment and placebo groups and subsetting the groups based on subject PRSS scores. Twenty items were selected for being predictive of patient global improvement rating, clinician global improvement rating, or improvement on Hamilton Rating Scale for Anxiety (HAM-A) scores in placebo-arm patients. Receiver operating characteristic concordance values ranged from 0.77 to 0.96 for the different definitions of placebo responder. A cut-score of 50 on a scale of 0-100 was chosen to maximize sensitivity (range 0.67-0.79) and specificity (range 0.78-1.00). Fifty-six patients with scores of 50 or higher were flagged as potential placebo responders. Excluding these 56 patients from the analysis resulted in a greater separation of active treatment from placebo. The PRSS is a promising tool for predicting placebo response in clinical trials and requires further use and validation.