In observational studies, high serum urate levels are associated with adverse outcomes, including mortality. However, the hypothesis that urate lowering may improve non-gout outcomes has not been confirmed by placebo-controlled clinical trials. On the contrary, seven recent placebo-controlled trials of urate lowering drugs with different mechanisms of action (uricosuric: lesinurad; xanthine oxidase inhibition: febuxostat; uricase: pegloticase) have observed higher mortality or trends to higher mortality in gout patients with the largest decreases in serum urate.