This randomized clinical trial aimed to determine whether daily d-mannose supplementation for 6 months reduces the proportion of women with recurrent urinary tract infections (UTIs) experiencing a medically attended UTI. The study was conducted in 99 primary care centers across the UK, recruiting 598 women aged 18 years or older who had a history of at least two UTIs in the preceding 6 months or three UTIs in 12 months. Participants were randomized to receive either 2 grams of d-mannose powder or an equal volume of placebo powder daily. The primary outcome measure was the proportion of women experiencing at least one further episode of clinically suspected UTI for which they contacted ambulatory care within 6 months. Secondary outcomes included symptom duration, antibiotic use, time to next medically attended UTI, number of suspected UTIs, and UTI-related hospital admissions. The results showed that the proportion of women contacting ambulatory care with a clinically suspected UTI was 51.0% in the d-mannose group and 55.7% in the placebo group, with a risk difference of −5% (95% CI, −13% to 3%; P = .26). There were no statistically significant differences in any secondary outcome measures between the two groups. The study concluded that daily d-mannose did not reduce the proportion of women with recurrent UTI in primary care who experienced a subsequent clinically suspected UTI, and it should not be recommended for prophylaxis in this patient group.This randomized clinical trial aimed to determine whether daily d-mannose supplementation for 6 months reduces the proportion of women with recurrent urinary tract infections (UTIs) experiencing a medically attended UTI. The study was conducted in 99 primary care centers across the UK, recruiting 598 women aged 18 years or older who had a history of at least two UTIs in the preceding 6 months or three UTIs in 12 months. Participants were randomized to receive either 2 grams of d-mannose powder or an equal volume of placebo powder daily. The primary outcome measure was the proportion of women experiencing at least one further episode of clinically suspected UTI for which they contacted ambulatory care within 6 months. Secondary outcomes included symptom duration, antibiotic use, time to next medically attended UTI, number of suspected UTIs, and UTI-related hospital admissions. The results showed that the proportion of women contacting ambulatory care with a clinically suspected UTI was 51.0% in the d-mannose group and 55.7% in the placebo group, with a risk difference of −5% (95% CI, −13% to 3%; P = .26). There were no statistically significant differences in any secondary outcome measures between the two groups. The study concluded that daily d-mannose did not reduce the proportion of women with recurrent UTI in primary care who experienced a subsequent clinically suspected UTI, and it should not be recommended for prophylaxis in this patient group.