Objectives: This study investigates common patterns in patients with exceptionally high creatine kinase (CK) levels to identify factors that could have contributed to the development of severe rhabdomyolysis in the studied cohort. Material and Methods: The authors present a retrospective analysis of patients with massive rhabdomyolysis (measured CK activity >50 000 U/l) caused by xenobiotics. The patients were selected from a group of 7708 patients treated at the Regional Toxicological Center. Results: The most frequent causative agents were recreational drugs, sedatives and anti-epileptics. Six patients developed multi-organ failure, including 1 who died. Substance abuse disorder was diagnosed in 90% of the patients. Each patient had at least 1 contributory factor present (hypothermia, hyperthermia, injury, an episode of agitation, seizures, prolonged immobilization), and the median was 3 factors. Acute kidney injury was observed in 90% of the patients, and 70% needed renal replacement therapy due to acute renal failure, which meant a longer hospital stay. Creatinine concentration differences between days 2 and 1 of the presentation (C_diff) correlated with the length of hospital stay (r = 0.73, p = 0.02). All patients with negative C_diff values did not need dialysis. No patients experienced liver failure. Conclusions: Massive rhabdomyolysis seems to be the effect of coincidence of several factors rather than the myotoxic effect alone. A creatinine concentration difference between days 2 and 1 of hospitalization was a good prognostic factor for the need for further dialysis. Int J Occup Med Environ Health. 2020;33(5):661–73