Background and Aim: Hospitalization of a preterm neonate is a major crisis for the involved family that significantly affects parents' quality of life. The main goal of empowerment programs is behavioral modification. The aim of this study was to assess the effects of an empowerment program on the knowledge, self-efficacy, self-esteem, and attitudes of the mothers of preterm neonates. Methods: This pretest-posttest quasi-experimental study was conducted in 2014 on a convenience sample of 30 mothers whose preterm neonates were hospitalized in the neonatal intensive care unit of Valiasr (PBUH) hospital, Birjand, Iran. An empowerment training program was implemented based on the personal empowerment model in seven 30-min personal face-to-face training sessions. The data were collected using a maternal and neonatal demographic questionnaire, a researcher-made knowledge and attitude questionnaire, the Vahdaninya and colleagues' self-efficacy questionnaire, and the Rosenberg Self-Esteem Scale. Finally, the data were entered into the SPSS software (v. 18.0) and described using the measures of descriptive statistics (such as mean and standard deviation). Besides, the normality of the variables was assessed through the Kolmogorov-Smirnov test, while the paired-sample t test was used to compare the pretest and posttest scores of knowledge, attitude, self-efficacy, and self-esteem at a significance level of 0.05.