There is growing interest in utilizing deep sedation with a natural airway rather than general endotracheal anesthesia (GETA) for cardiac catheterization procedures due to the presumed hemodynamic benefits and faster postprocedural recovery, although a paucity of data supports these assumptions. We hypothesized that the periprocedural complication rate would be lower in patients undergoing transcatheter pulmonary valve implantation (TPVI) under deep sedation with a natural airway versus those under GETA. We performed a retrospective chart review of 85 patients undergoing isolated TPVI at a large academic medical institution. A logistical regression adjusting for age was performed. The primary outcome was periprocedural complication rate, including access site rebleeding, hematoma, conversion to GETA, arrhythmia requiring intervention, cardiac arrest, blood transfusion, and postoperative nausea and vomiting. Significantly more patients in the GETA group experienced complications compared with the deep sedation group (41.2% vs 14.7%, P = .015). The secondary outcomes included vasopressor use, recovery location, and procedural, anesthesia, and recovery times. The median procedure time was shorter in the sedation group by 38 minutes (P = .010), and anesthesia time was shorter by 50 minutes (P = .001). Overall, we found that deep sedation is feasible for TPVI and in this retrospective study was associated with decreased periprocedural complications.