Background: We developed an indicated preventive life-review course, “Looking for Meaning”, based on the assumption that reminiscence styles influence coping with depressive symptoms. This study describes the impact of this course in a pragmatic randomized controlled trial. Methods: Inclusion criteria were >50 years, a score of 5 or higher on the Center for Epidemiological Studies Depression Scale (CES-D), and no depressive disorder or psychotropic or psychological treatment. Participants were randomized and stratified by gender: the experimental group (N = 83) was offered the course and the comparison group (N = 88) a movie. There were three measurements: pre-treatment, post-treatment and 6 months after post-treatment. Depressive symptoms constituted the primary outcome. Secondary outcomes were anxiety symptoms, satisfaction with life, mastery and reminiscence styles. All analyses were conducted according to the intention-to-treat principle. Missing values were replaced by regression imputation. Results: The course reduced depressive symptoms, a decrease that was retained during follow-up. A significant between-group effect size was found (d = 0.58). There was also a reduction in symptoms of anxiety; however, the comparison group showed the same reduction, resulting in a small between-group effect size. Gender and level of depressive symptoms were found to be prognostic factors for the change in depressive symptoms; age was not. Post hoc analyses showed significant between-group effect sizes for females and those with a score above the cut-off of the CES-D. Conclusion: The course “Looking for Meaning” can be recommended for people aged over 50 years, females and older adults with a clinically relevant level of depressive symptoms (above cut-off) in particular.