Awake craniotomy is the gold standard for the resection of brain lesions near eloquent areas. For the commonly used asleep-awake-asleep technique, the patient must be awake and fully cooperative as soon as possible after discontinuation of anesthetics. A shorter emergence time is essential to decrease the likelihood of adverse events. Previous research found no relationship between body mass index (BMI) and time-to-awake for intravenous anesthesia with propofol, which is a lipophilic agent. As BMI cannot differentiate between fat and muscle tissue, we hypothesize that skeletal muscle mass, particularly when combined with BMI, may better predict time-to-awake from propofol sedation. We aimed to evaluate the relationship between skeletal muscle mass and the time-to-awake in patients undergoing awake craniotomy, as well as the interaction between skeletal muscle mass and BMI. In 260 patients undergoing an awake craniotomy, we used preoperative magnetic resonance imaging to assess temporalis muscle and cross-sectional skeletal muscle area of the masseter muscles and at level of the third cervical vertebra. Time-to-awake was dichotomized as ≤20 and >20 minutes. No association between various measures of skeletal muscle mass and time-to-awake was observed, and no interaction between skeletal muscle mass and BMI was found (all P > .05). Likewise, patients with a high BMI and low skeletal muscle mass (indicating an increased proportion of fat tissue) did not have a prolonged time-to-awake. Skeletal muscle mass did not predict time-to-awake in patients undergoing awake craniotomy, neither in isolation nor in combination with a high BMI.