Flare of acne is common at the beginning of isotretinoin treatment. However, severe flare is rare. Multiple comedones, male gender and young age are reported as promoting factors. However, detailed information is still limited. Our aim was to investigate the incidence, types and course of acne flare and the predictive factors for its occurrence. 244 patients were enrolled. Acne grade was defined according to global acne grading system (GAGS) score. Flare was classified according to the increase in number of inflammatory nodules and treatment requirements of the patients. Risk factors (age, sex, duration of acne, basal acne grade, baseline numbers of comedones, papule-pustules, nodules, hyperandrogenism, and presence of sinuses) were investigated. 161 patients completed the study. 79 patients (32%) had facial and/or truncal flare. Flare was mild in 18% (n = 44), moderate in 10% (n = 24), and severe in 4.5% (n = 11) of the patients. For severe flare, male sex, severe acne, GAGS cut-off score greater than 28, presence of more than 44 facial comedones and 2 facial nodules and presence of truncal nodules were found to be predictive. Recognizing predictive factors for severe flare may help to take early precautions and to prevent severe flares which may result with permanent scars.