e18574 Background: ND has historically been recommended to reduce infectious complications in cancer patients (pts). While the adoption of ND has declined over the last decade, recent studies - particularly in pts undergoing hematopoietic stem cell transplantation (HSCT) - have raised uncertainty regarding the safety of LD. Herein, we performed a meta-analysis of studies directly comparing ND with LD in pts with cancer. Methods: We conducted a systematic search of MEDLINE, Embase, and Cochrane databases from inception through January 2026. Comparative retrospective and prospective studies were included if they were comparing ND with LD in adults or children with cancer. Primary outcomes were major infections and bacteremia/fungemia. Secondary outcomes were pneumonia, diarrhea, and all-cause mortality. Random-effects meta-analyses were performed to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). The review followed PRISMA 2020 guidelines. Results: Fifteen studies enrolling 4,320 patients were included in the primary analysis. Six studies enrolled only adult patients, three were restricted to pediatric populations, and six included mixed adult and pediatric cohorts. Across these studies, ND was not associated with a significant reduction in major infections (RR 1.02, 95% CI 0.88–1.18; p=0.795), bacteremia/fungemia (RR 0.97, 95% CI 0.78–1.22; p=0.805), pneumonia (RR 0.98, 95% CI 0.59–1.63; p=0.933), diarrhea (RR 1.12, 95% CI 0.96–1.31; p=0.159), or all-cause mortality (RR 0.94, 95% CI 0.77–1.15; p=0.632). Sensitivity analyses restricted to RCTs showed consistent results. Subgroup analysis of hematological/HSCT studies (9 studies; 1,769 pts) also showed no differences across outcome. Analysis restricted to RCTs in hematologic/HSCT pts (6 studies; 855 pts) showed no differences in major infections, pneumonia, diarrhea, or mortality; however, ND was associated with a lower risk of bacteremia/fungemia (RR 0.67, 95% CI 0.47–0.95; p=0.023). Heterogeneity across studies was low to moderate. Conclusions: ND was not associated with reductions in major infections, pneumonia, diarrhea, or mortality compared with LD. A reduction in bacteremia/fungemia was observed in RCTs of hematologic malignancy and HSCT pts. Overall, these findings suggest that routine ND implementation is unnecessary for most cancer pts, although cautious dietary practices may remain reasonable in selected high-risk hematologic malignancy/HSCT populations.