There has been a growing demand for teacher training institutions to equip pre-service teachers with practical skills that can enhance their teaching performance. In Biology teacher education, experiments have been employed with the educational approach to compensate for inadequate classroom-only instruction. This study aimed to assess the effectiveness of an intervention using biological experiments in developing experiment skills of pre-service teachers of Biology in Vietnam. The study also aimed to identify the challenges to the acquisition of experiment skills faced by Vietnamese pre-service teachers. A group of 128 pre-service teachers from four teacher-training institutions participated in the experimental courses. Pre-service teachers’ improvement in terms of knowledge of the subject matter and experiment skills throughout the experimental courses was evaluated using pre-tests, progress tests, post-tests, and observations The results showed significant improvements in the performance of pre-service teachers as they were provided with an increasing amount of experiment practices. This indicated the effectiveness of training pre-service teachers to acquire experiment skills for their future teaching practices and supported the need to incorporate experiment training in teacher education curricula. Meanwhile, interviews with teacher trainers and pre-service teachers after the experimental courses revealed four major obstacles to the acquisition of experiment skills, namely school, curriculum, teacher trainer and pre-service teacher factors.