OBJECTIVE To determine the relative cost effectiveness of long term rotational antibiotics and isotretinoin for moderate/severe acne over a 5-year period.DESIGN Retrospective study of pairs of patients matched for age, sex, acne severity and duration of acne.SETTING Teaching hospital dermatology out-patient department.SUBJECTS A group of 100 patients under long-term assessment for relapse rate following isotretinoin treatment were matched against a group of 100 similar patients who were given long-term antibiotics.MAIN OUTCOME MEASURE Prescribing costs and costs of out-patient visits. Costings were derived for dispensing from hospital (isotretinoin and antibiotics) or the community (antibiotics).RESULTS The mean duration of courses of isotretinoin was 19 weeks compared with 64.4 months for courses of rotational antibiotics and topical medication. Isotretinoin produced more than 60% improvement in 88% of patients, while only one patient in the antibiotic group improved by more than 50% of the initial acne severity and 34% suffered deterioration of acne over the 5-year treatment period. The median cost of isotretinoin and any additional acne treatment was£650 (±£65.16 (95% ci)) and the mean cost of rotational antibiotics was£1863 (±£56.80) if dispensed from the hospital pharmacy or£2108 (±£61.10) if dispensed in the community. These differences were highly significant (p<.001).CONCLUSION A single course of isotretinoin was much more effective than any equivalent course of antibiotics although more expensive. For the treatment of moderate/ severe acne, isotretinoin proved to be significantly more cost effective than long term rotational antibiotics over the 5-year period of observation. There is, therefore, not only a great personal saving in terms of distress and discomfort, but also an important global saving in financial terms from using isotretinoin rather than long-term rotational antibiotics. In addition, there were significant differences between hospital- and community-based dispensing of antibiotics and topical preparations for acne.