Background: Isotretinoin has been proven to be an effective treatment for acne vulgaris. The enclosed package insert with isotretinoin suggests weekly/biweekly laboratory testing (hepatic functions and lipid analysis) but fails to recommend the needed action levels for abnormalities. Methods: We provide a statistical analysis of a retrospective study of 141 individuals’ course of therapy on isotretinoin and their laboratory blood analysis results. Results: Very few statistically significant elevations in liver enzymes or lipid profiles occurred. More importantly, in only 1 case did these elevations warrant the discontinuation of therapy. Conclusion: The data presented here support the conclusion that limited blood testing should be performed for most patients and that more complete blood testing be done only for those patients with a significant response in liver enzymes, cholesterol or triglycerides. A set of guidelines is proposed for the practicing physician to interpret blood test results.