Simple SummaryUlceration of the stomach, also known as Equine Gastric Ulcer Syndrome (EGUS), is common in Thoroughbred racehorses. Ulceration can affect the upper (squamous) or lower (glandular) portion of the stomach with prevalence up to 100% and 25–72%, respectively, reported in racing populations. Omeprazole, a potent proton pump inhibitor drug, is widely used to treat this condition, with recommended withholding periods (RWPs) for racing varying from ‘not on race day’ to ‘2 clear days’. A rebound increase in gastric acid occurs in humans when acid-suppressing therapy with omeprazole ceases and might result in ‘rebound ulcers’. We hypothesized a similar phenomenon in horses if omeprazole treatment ceases in accordance with the RWPs for racing. We studied the effect of ‘not on race day’ (RWP0) and ‘2 clear days’ (RWP2) RWPs on the recurrence of EGUS in Thoroughbred horses in race training. Horses received a standard treatment course of omeprazole and were assessed by gastroscopic examination throughout the study. The prevalence of squamous ulceration was greater in horses subjected to an RWP2, although the effect was partially mitigated by the administration of a nutraceutical supplement, indicating potential implications of RWPs on the welfare and performance of Thoroughbred racehorses.AbstractThe impact of recommended withholding periods (RWPs) for omeprazole on the recurrence of Equine Gastric Ulcer Syndrome (EGUS) is unknown. The study was designed to compare the effect of two RWPs on EGUS recurrence post-omeprazole treatment and to determine if a nutraceutical supplement would reduce EGUS recurrence when administrated during an RWP. The study was a blinded, randomized clinical trial. Part 1: Horses were allocated to an RWP0 or RWP2 and crossed over after 4-weeks. Horses received oral omeprazole once daily, except during the RWPs at the end of the treatment periods. Part 2: Horses received omeprazole for 21 days prior to an RWP2 during which they received a nutraceutical supplement. Gastroscopy was performed on Day 0 and pre- and post- RWP. Part 1: More horses were affected by Equine Squamous Gastric Disease (ESGD) after the ‘2-clear-days’ RWP than the ‘not on race-day’ RWP (p= 0.012). The prevalence of ESGD post-RWP for ‘2-clear-days’ did not differ from day 0 (p= 0.478). Part 2: The prevalence of ESGD post-RWP was lower than on Day 0 (p= 0.046). A difference in recurrence of ESGD was present between the two common RWPs. The implications of this on the welfare of Thoroughbred racehorses warrant further discussion.