Acne vulgaris, usually just referred to as acne, is the most common skin disease. It causes red spots, pus‐filled spots and blackheads and can vary in severity from mild to severe. Because it can be very visible, it can cause anxiety, reduced self‐esteem and stigma. In cases of more severe acne that hasn't improved with other treatments, a powerful drug taken orally (by mouth) called isotretinoin can be prescribed by doctors. This study, from Canada, reviewed evidence from randomized controlled trials (RCTs) to assess the efficacy and safety of isotretinoin. RCTs are studies in which a number of patients are randomly allocated to two or more test groups, one of which will be a ‘control’ group (who typically receive either no treatment, standard care or a placebo), while the other groups will receive the specific treatments being tested. The different groups of patients are then monitored in the exact same way, allowing for direct comparison between different treatments. Eleven trials were identified, involving a total of 760 patients ‐ mostly males. Across all trials, isotretinoin reduced acne lesion counts (number of spots), and always by a greater amount than controls, which were either placebo, oral antibiotics, or another control type. The frequency of adverse events, meaning unwanted side effects, was twice as high with isotretinoin (751 events) compared to control (388 events). More than half of all adverse events related to skin dryness. Adverse events caused 12 of the 760 participants to withdrawal from trials, due to the development of Stevens‐Johnson Syndrome, cheilitis, xerosis, acne flare, photophobia, elevated liver enzymes, decreased appetite, headaches and depressed mood. This review suggests that isotretinoin is effective in reducing acne lesion counts, but adverse events are common.