Background: This study aims to define the incidence and risk factors of both emergence agitation and hypoactive emergence in adult patients and substance-dependent patients following general anesthesia to elaborate on the risk factors and precise management of them. Methods: The study recruited 1,136 adult patients who received elective surgeries under general anesthesia for this prospective observational study. Inadequate emergence was determined according to the Richmond Agitation-Sedation Scale (RASS). Emergence agitation was defined as a RASS ≥ +1 point, and hypoactive emergence was defined as a RASS ≤ –2 points. Subgroup analyses were then conducted on patients with substance dependence. Results: Inadequate emergence in the post-anesthesia care unit (PACU) occurred in 20.3% of patients, including 13.9% with emergence agitation and 6.4% with hypoactive emergence. Ninety-five patients had a history of substance dependence. Compared to divorced patients, never-married and presently married patients, who underwent gynecological and thoracic surgeries, had a lower risk of agitation. Neurologic disorders, intraoperative blood loss, intraoperative morphine, and PACU analgesic drug administration were associated with increased agitation risk. Hypertension and psychological disorders, intraoperative opioids, and PACU Foley catheter fixation were associated with increased hypoactive emergence risk. Substance-dependent patients had higher risk for agitation (21.1%, P = 0.019) and hypoactive emergence (10.5%, P = 0.044). Conclusions Inadequate emergence in PACU following general anesthesia is a significant problem correlated with several perioperative factors. Patients with a history of substance dependence appear to be more at risk of inadequate emergence than the general population.