Effective treatments for major depressive disorder exist, yet some patients fail to respond, or achieve only partial response. One approach to optimizing treatment success is to identify which patients are more likely to respond best to which treatments. The objective of this investigation was to determine if patient personality characteristics are predictive of response to either cognitive-behavioural therapy (CBT) or pharmacotherapy (PHT). Depressed patients completed the Revised NEO Personality Inventory, which measures the higher-order domain and lower-order facet traits of the Five-Factor Model of Personality, and were randomized to receive either CBT or PHT. Four personality traits-the higher-order domain neuroticism and 3 lower-order facet traits: trust, straightforwardness, and tendermindedness-were able to distinguish a differential response rate to CBT, compared with PHT. The assessment of patient dimensional personality traits can assist in the selection and optimization of treatment response for depressed patients.