Abstract Background The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed younger than age 50 years has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints. Methods In a prospective cohort study (Nurses’ Health Study II), we evaluated 2 empirical dietary patterns (Western and prudent) and 3 recommendation-based indexes (Dietary Approaches to Stop Hypertension [DASH], Alternative Mediterranean Diet [AMED], and Alternative Healthy Eating Index [AHEI]-2010) with risk of early-onset adenoma overall and by malignant potential (high-risk: ≥1 cm, tubulovillous or villous histology, high-grade dysplasia, or ≥3 adenomas), among 29 474 women with 1 or more lower endoscopy before age 50 years (1991–2011). Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results We documented 1157 early-onset adenomas with 375 at high risk. Western diet was positively associated, whereas prudent diet, DASH, AMED, and AHEI-2010 were inversely associated with risk of early-onset adenoma. The associations were largely confined to high-risk adenomas (the highest vs lowest quintile: Western, OR = 1.67, 95% CI = 1.18 to 2.37; prudent, OR = 0.69, 95% CI = 0.48 to 0.98; DASH, OR = 0.65, 95% CI = 0.45 to 0.93; AMED, OR = 0.55, 95% CI = 0.38 to 0.79; AHEI-2010, OR = 0.71, 95% CI = 0.51 to 1.01; all Ptrend ≤ .03), driven by those identified in the distal colon and rectum (all Ptrend ≤ .04, except AMED: Ptrend = .14). Conclusion Poor diet quality was associated with an increased risk of early-onset distal and rectal adenomas of high malignant potential. These findings provide preliminary but strong support to the role of diet in early-onset CRC.