Objective: To quantify the efficacy of a siderophore receptor and porin (SRP) proteins-based vaccine on the burden of Escherichia coli O157:H7 in feedlot cattle. Methods: Two research trials were conducted in field conditions. In each trial, cattle (n=1252 in trial #1; n=1284 in trial #2) were systematically divided into 20 pens and were administered either the E. coli O157 SRP vaccine or a placebo (trial #1: days 0 and 21; trial #2: days 0, 21, and 42). Rectal fecal samples were collected on day 0, and pen floor samples were collected on days 21, 35, 70, and 85 for trial #1 and on days 42 and 98 for trial #2. On day 85 of trial #1, rectoanal mucosal swab samples and hide swab samples were collected. Cattle were weighed on days 0, 21, and 85 (trial #1) or 1 week before harvest (trial #2). Results: In trial #1, prevalence of E. coli in the feces was lower in vaccinates compared to control animals (p=0.04). On day 85, the likelihood of an animal being positive at any site was less among vaccinates than controls (p=0.02). In trail #2, vaccination with SRP was associated with reduced shedding by 85.2% on day 98 (p<0.01) but not on days 0 or 42. Vaccination with SRP was associated with a 98.2% reduction in concentration of E. coli O157 in fecal samples (2.54 vs. 0.80 log MPN/g of feces; p<0.01). Cattle performance was not affected by SRP administration. Conclusions: The E. coli O157:H7 SRP-based vaccine might serve as a preharvest intervention to reduce the burden of E. coli O157:H7 on cattle presented for harvest.