Small-leaf spiderwort (Tradescantia fluminensis Vell.) is a low-growing perennial ground cover that has become increasingly problematic in Florida due to its ability to quickly spread vegetatively over large areas and outcompete native vegetation. Prior research has identified several herbicides that can be used to manage T. fluminensis, but the effect of application timing on herbicidal efficacy is unknown. Therefore, the objective of this study was to evaluate the efficacy of selected postemergence herbicide applications and to understand differences in the efficacy of these timings (i.e., spring and fall), including on the rate of regrowth of target plants. Specific herbicides evaluated in this study included 2,4-D, 2,4-D + triclopyr amine, aminopyralid, glyphosate, and triclopyr (as acid and amine). An additional aspect of this study was to reapply treatments when coverage ratings exceeded 25% to assess the impact of sequential applications when using less efficacious herbicides that might provide greater selectivity to non-target plants. Overall, the data showed that initial treatment timing had little to no impact on efficacy for most of the herbicides evaluated. Triclopyr (acid or amine) tended to provide the highest level of control and required no retreatment over a 12-mo evaluation period. Other effective options included glyphosate and 2,4-D + triclopyr amine, which provided results similar to triclopyr on most evaluation dates. The 2,4-D and aminopyralid treatments were in general the least efficacious options, requiring retreatment at either 3, 6, or 9 mo following the initial application to achieve less than 25% T. fluminensis coverage. Results indicate that practitioners would likely achieve similar levels of T. fluminensis control regardless of application timing. Data also suggest triclopyr would be the most effective option, while a low level of control would be expected with 2,4-D, even following multiple applications.