OBJECTIVE: To determine whether problem-solving treatment (PST) can prevent depressive disorders in patients with age-related macular degeneration (AMD). DESIGN: Two hundred six patients with AMD were randomly assigned to PST (n = 105) or usual care (n = 101). PST therapists delivered six PST sessions over 8 weeks in subjects' homes. MEASUREMENTS: Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition Diagnoses of Depressive Disorders, Hamilton Depression Rating Scale scores, and rates of relinquishing valued activities were assessed at 2 months for short-term effects and 6 months for maintenance effects. RESULTS: The 2-month incidence rate of depressive disorders in PST-treated subjects was significantly lower than controls (11.6% versus 23.2%, respectively; OR = 0.43; 95% CI [0.20, 0.95]). PST also reduced the odds of relinquishing a valued activity (OR = 0.48; 95% CI [0.25, 0.96]); this effect mediated the relationship between treatment group and depression. By 6 months most earlier observed benefits had diminished. Secondary analyses showed that a minimal level of depressive symptoms were disabling and predicted incident depressive disorders. CONCLUSION: PST prevented depressive disorders and loss of valued activities as a short-term treatment but these benefits were not maintained over time. To sustain PST's effect, an intervention that uses a problem-solving framework to enhance rehabilitative skills may be necessary.