Abstract The objective of this study was to determine the prevalence and describe the factors associated with off-label drug use in an adult intensive care unit (ICU) of a Brazilian hospital. An analytical, cross-sectional, prospective study was conducted in the adult ICU population from March 2018 to May 2018. Off-label use of medication was classified by indication, dosage, route of administration, type and volume of diluent, and duration of administration. Most patients were female (57.89%), non-elderly (56.14%), and had a mean age of 54.44 ± 17.15 years. The prevalence of off-label drug use was 70.31%, but was not associated with the clinical severity of the patients. A statistically significant association was observed between label use of drugs and prescribing potentially inappropriate medicines (PIM). The most common reasons for off-label drug use were therapeutic indication (19.58%) and volume of diluent (23.30%). Drug administration by enteral tubes accounted for the largest number of off-label uses due to route of administration (90.85%). There was a higher prevalence of off-label use of systemic antimicrobials (14.44%) and norepinephrine (9.28%). Our study provided a broad characterization of off-label drug use in an adult ICU and showed why it is important for health professionals to evaluate the specific risks and benefits of this practice