Abstract Studies suggested a positive association between ultra-processed food (UPF) intake and risk of type 2 diabetes (T2DM). However, the magnitude of association varies across studies due to differences in population characteristics and methodological issues. It is also unclear about the exact shape of the association and whether the association is independent of diet quality and adiposity. We conducted a dose-response meta-analysis of prospective studies to summarize the association between UPF intake and T2DM risk. PubMed/MEDLINE, Web of Science, and Embase were searched through Jan. 2024 to identify relevant studies. Using random-effects models, summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated for each of the following unit increment in UPF intake: 10% (of total g/d), 100-g/d, and 1-serving/d. A non-linear dose-response meta-analysis was conducted using restricted cubic spline analysis. After screening 569 publications, 12 prospective cohort studies were included in this study. The summary RRs associated with every 10%, 100-g, and 1-serving increment in UPF intake were 1.13 (95% CI = 1.10-1.16), 1.05 (95% CI = 1.03-1.06), and 1.04 (95% CI = 1.03-1.05), respectively. The positive associations remained statistically significant after additional adjustment for diet quality, BMI, and total energy intake. The dose-response curve for g/d of UPF intake suggested evidence of nonlinearity (p-nonlinearity=0.0005), showing a steeper increase in risk at UPF intake >300 g/d. However, evidence for non-linearity was not observed with % and serving/d of UPF intake. The association did not significantly vary by method and timing of UPF assessment. Higher summary RRs were observed among studies from Europe and North America compared with those from other countries (p-heterogeneity=0.048). Our data suggest that higher UPF intake may increase T2DM risk, independent of diet quality and adiposity. Key messages • Higher intake of ultra-processed food is positively associated with the risk of type 2 diabetes. • Public health strategies should encourage healthier dietary choices by emphasizing reduction of UPF intake in dietary guidelines and implementing regulations on manufacturing and labeling of UPF.