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Using the General Practice Research Database, the authors performed (1) a cohort analysis comparing the incidence of liver dysfunction in new users of minocycline with new users of oxytetracycline/tetracycline and (2) a case control study assessing antibiotic exposure in new cases of liver dysfunction and controls without liver dysfunction. In new users, the incidence of liver dysfunction in those exposed to minocycline was 1.04 cases/10,000 exposed person months (EPM) and 0.69 cases/10,000EPMin those exposed to oxytetracycline/tetracycline (relative risk 1.51 [CI95: 0.63, 3.65]). The risk in both groups was greatest in the first month of use. The adjusted odds ratio (ORadj) of liver dysfunction associated with exposure to minocycline compared with nonuse was 2.10 (CI95: 1.30, 3.40); for oxytetracycline/tetracycline, the ORadj was 1.46 (CI95: 0.81, 2.64); and for exposure to erythromycin, the ORadj was 1.64 (CI95: 0.71, 3.80). The authors thus support a weak association between the use of oral antibiotics and liver dysfunction in patients with acne. The risk associated with exposure to minocycline appears to be very small. The cohort analysis demonstrated that any risk associated with minocycline was not significantly greater than that associated with oxytetracycline/tetracycline exposure.