Background <p>The long-term effects of Percutaneous Endoscopic Gastrostomy (PEG) versus Nasogastric Tube (NG) placement on adult mortality and aspiration pneumonia are debated. This study aimed to compare these long-term risks using a large, multi-institutional retrospective database.</p> Methods <p>This retrospective cohort study used de-identified data from the TriNetX US Collaborative Network (2005–2024). Adults undergoing PEG or NG tube placement were propensity score-matched (1:1), although swallowing study results were unavailable for matching. Primary outcomes over a 10-year follow-up were incident aspiration pneumonia and all-cause mortality. Analyses included Cox proportional hazards models, landmark analyses, and stratified analyses by NG tube placement frequency.</p> Results <p>Among 34,539 matched pairs, PEG was associated with lower observed 30-day all-cause mortality (HR 0.53, 95% CI 0.51–0.56) but higher mortality during 31–365 days (HR 1.70, 1.59–1.81) and 1–10 years (HR 1.57, 1.49–1.65). In the overall matched cohort, PEG was associated with a higher long-term aspiration pneumonia risk (HR 1.66, 1.56–1.75). When stratified by NG tube placement frequency, the between-group mortality difference attenuated from HR 1.16 (1.12–1.19) at one placement to HR 0.74 (0.65–0.86) at ≥ 5 placements. The aspiration pneumonia association attenuated but remained statistically significant across all strata.</p> Conclusion <p>PEG was associated with a higher overall observed risk of aspiration pneumonia; however, this association attenuated with increasing NG tube placement frequency, and the observed mortality difference was no longer statistically significant among patients with repeated NG tube placements. These observational associations may reflect differences in NG tube placement frequency and clinical context within the comparator group, and may offer a clinical reference for tube access selection in similar patients.</p>