BACKGROUND AND OBJECTIVES: Major depressive disorder is one of the most common psychiatric disorders in patients with acne. The objective was to assess the association between acne and depression. METHOD: We performed a case-control study in a private outpatient clinic in Santiago, Chile. The case group was composed of adult patients attending our center with a clinical diagnosis of acne, established by an experienced dermatologist. The control group consisted of adult patients without acne who were related to subjects in the case group. Cases and controls were matched by sex, age and socioeconomic status. To measure depressive disorder, the Compound International Diagnostic Interview (CIDI) was applied to both groups. All the numerical variables were compared with Student's t-test and categorical variables were compared with the χ2 test and odds ratios. RESULTS: Sixty patients were included (30 in each group): 21 females and nine males. All patients completed the questionnaire. No significant differences were found between the two groups in any of the demographic variables analyzed. In the case group, nine patients (30%) met the diagnostic criteria for major depressive disorder, whereas only two patients (6.6%) in the control group met these criteria (OR = 6; 95% confidence interval, 1.03-45.22; p = 0.02). CONCLUSIONS: We found a statistically significant association between major depressive disorder and acne. The risk of depression was approximately 6 times greater in patients with this disorder.