OBJECTIVES: Previous studies have shown associations between isotertinoin treatment and inflammatory bowel disease (IBD) and suspected that acne treatment with isotertinoin carries an increased risk of developing IBD. The association between acne drug therapy and incidence of IBD with adjustment of potential confounders, however, remains unclear. This study evaluated the effects of drug therapies on the development of IBD in acne patients. METHODS: A longitudinal retrospective study was conducted using the 2003-2007 MarketScan Medicaid Claims dataset representing 176,889 eligible patients with acne vulgaris. The Cox proportional-hazard survival analysis was performed to obtain the hazard ratios (HRs) of IBD development, adjusting age, race, sex, physician specialty, Charlson Comorbidiy index (CCI), cumulative dosage of isotretinoin and acne drug treatment. RESULTS: A total of 492 of the patients had an IBD occurrence within the study period. Black patients had lower hazard of developing IBD than white patients (p<0.01). Compared with adults, youths and children were less likely to have an IBD occurrence (all p<0.01). Patients seen by dermatologists are associated with a 51% higher hazard of developing IBD (p<0.01). Patients whose acne was treated with oral antibiotics, topical antibiotics, or topical glucocorticoids were less likely to develop IBD (HRs=0.45, 0.42, 0.51, respectively; all p<0.05) compared with those without these drugs. Patients with a higher cumulative dosage of isotretinoin treatment had an 87% lower hazard of developing IBD (HRs=0.13; p<0.05). A unit increase in CCI was associated with a 17% higher hazard of IBD incidence (p<0.01).  CONCLUSIONS: The likelihood of IBD occurrence in acne patients treated with drug therapy varied with age and race, consultation with dermatologists, and acne medication. The higher cumulative dosage of isotretionin treatment was associated with a lower risk of developing IBD. With adding confounding controls to the analysis, the relationship between isotretionin treatment and IBD development reveals different results from previous studies.