Objective: The purpose of this study was to identify the prognostic factors for individuals with mechanical neck pain likely to experience improvements in both pain and disability after the application of an intervention including cervical and thoracic spine thrust manipulations. Methods: Patients presenting with mechanical neck pain participated in a prospective single-arm trial. Participants underwent a standardized examination and then received a series of thrust manipulations directed toward the cervical, cervicothoracic, and thoracic spine. Participants were classified as having achieved a successful outcome at the second and third sessions based on their perceived recovery. Potential prognostic variables were entered into a stepwise logistic regression model to determine the most accurate set of variables for the prediction of treatment success. Results: Data from 81 subjects were included in the analysis, of which 50 experienced a successful outcome (61.7%). Five variables including pain intensity greater than 4.5 points; cervical extension less than 46; presence of hypomobility at T1; a negative upper limb tension test and female sex were identified. If 4 of 5 variables were present (likelihood ratio, +1.9), the likelihood of success increased from 61.7% to 75.4%. Conclusions: This study identified several prognostic clinical factors that can potentially identify, a priori, patients with neck pain who are likely to experience a rapid response to the application of an intervention including both cervical and thoracic spine manipulations. However, no combination of the variables was able to dramatically increase the posttest probability. (J Manipulative Physiol Ther 2011; 34: 144-152)