The onset of antidepressant action is vital clinically. This study aimed to testify whether early symptom improvement can predict eventual treatment response at week 6 among depressive hospitalized patients taking fluoxetine. One hundred thirty-one hospitalized patients with major depressive disorder received 20 mg/d of fluoxetine for 6 weeks. Symptom severity was assessed by the 17-item Hamilton Depression Rating Scale (HAMD-17) at weeks 0, 1, 2, 3, 4, and 6. Stable response was defined as a reduction of 50% or more in the HAMD-17 total score at weeks 4 and 6 of treatment. Receiver operating characteristic curve was used to determine the cutoff point of the percentage of HAMD-17 score reduction between stable responders and nonresponders at weeks 1, 2, 3, and 4. At weeks 1, 2, 3, and 4, HAMD-17 score reductions of 25%, 39%, 43%, and 50% seemed to be the optimal cutoff points for predicting eventual response. They provided a sensitivity of 78%, 86%, 91%, and 93% and a specificity of 61%, 74%, 76%, and 92%. The percentage of HAMD-17 reduction at week 4 excellently predicted final response at week 6. Patients with less than a 50% symptom reduction during the first 4 weeks of treatment are unlikely to reach a final stable response. Whether this model can be applied to establish a prediction system for other antidepressants or for outpatients warrants further research.