Levothyroxine (LT4) suppressive therapy for solitary thyroid nodules is not popularly advocated presently because its clinical efficacy and safety are currently considered controversial. This meta-analysis aims to address efficacy issues by using rigorous methods to arrive at a pooled estimate. On the basis of the analysis, it is estimated that LT4 therapy is clearly associated with up to a two-fold increase in the chance of nodule reduction. This translates to a number needed to treat (NNT) of 6 or a 50% decrease in the risk of cancer given nodule reduction. Keeping this definition of efficacy in mind and a low incidence of adverse events with low level LT4 suppression, such an intervention might be appropriate in patients selected on the basis of a low risk for adverse effects.