English for Library Science is an essential course for students to command comprehensive scope of library knowledge. This study aims to compare the learning outcomes, gender differences and affective factors in the environments of blended and traditional learning. Around one thousand participants from one university were randomly selected to answer questions in questionnaires. It was found that (1) the pass rates under blended learning increased compared with traditional multimedia learning and the dropout rates under blended learning decreased compared with multimedia learning; (2) males and females did not show any significant differences in learning outcomes; (3) affective factors under blended learning were significantly more favorable than those under multimedia learning; and (4) under the blended learning model, male motivation was significantly higher than female; male attitude was significantly more favorable than female; males held higher self-esteem than females. However, male anxiety was significantly less than female. Reasons for the findings, as well as future research direction, were also explored.