The rescue, rehabilitation, and release of Florida manatees (Trichechus manatus latirostris) into the wild has occurred since 1974; however, a comprehensive evaluation of the outcomes of the releases has never been conducted. Herein, we examined data for 136 Florida manatees that were rehabilitated and released with telemetry tags between 1988 and 2013 to determine release outcome of each individual as either success (acclimation) or failure after at least 1 y. Ten predictor variables were statistically evaluated for potential relationships to release outcome. To assess the contribution of each predictor variable to release outcome, each variable was tested for significance in univariate analyses. Manatees born in captivity experienced poor success after release (14%), whereas the overall success of wild-born individuals was higher (72%). When compared with other variables in our dataset, number of days in captivity was the strongest predictor for determining success. Manatees rescued as calves and held in captivity for more than 5 y had a high likelihood of failure, while subadults and adults had a high likelihood of success, regardless of the amount of time spent in captivity. Ensuring the success of individual manatees after release is critical for evaluating the contribution of the manatee rehabilitation program to the growth of the wild population.