Background/Objectives: The administration of propofol without an anesthesiologist (NAAP) during endoscopic procedures is generally considered safe. However, the available data remain limited and fragmented due to legal constraints. This systematic review and meta-analysis aimed to evaluate the incidence of adverse events in adults undergoing procedural sedation with NAAP. Methods: A comprehensive search was conducted in three electronic databases (MEDLINE, EMBASE, and the Cochrane Library) for studies published between 2010 and 2023. Eligible studies included randomized controlled trials and observational studies that reported predefined adverse events in adult patients receiving NAAP for procedural sedation. The analysis encompassed various types of endoscopic procedures and sedation protocols, including both balanced sedation and propofol monotherapy. Clinical heterogeneity was assessed by comparing patient characteristics, sedation methods, and outcome measures across studies. A random effects model was used for the meta-analysis, with results presented as estimated incidence rates. Subgroup analyses were conducted based on the hypoxia severity, sedation approach, and procedure type. Results: The search yielded 2963 records, of which 73 studies met the inclusion criteria, covering a total of 967,238 procedural sedations. Hypoxia was the most frequently reported adverse event, occurring in 40‰ of cases, followed by hypotension (38‰) and bradycardia (9‰). Severe adverse events requiring emergency intervention were rare, with an incidence of 0.12‰. The subgroup analysis indicated a low occurrence (6‰) of severe desaturation (SpO₂ < 80%) and no significant differences in adverse event rates between balanced propofol sedation and propofol-only sedation. However, advanced endoscopic procedures (EUS, ERCP, PEG, enteroscopy, EMR/ESD) were associated with a higher risk of hypoxia (10% vs. 26‰; p < 0.00001) and major complications (3.1‰ vs. 0.1‰; p = 0.015) compared to diagnostic procedures. Conclusions: NAAP-based procedural sedation appears to be generally safe. While the minor adverse event rates vary depending on the sedation regimen and procedure type, major complications remain exceptionally rare.