Medical students often have initial understanding concerning medical domains, such as the central cardiovascular system (CCVS), when they enter the study programme. These notions may to some extent be in conflict with scientific understanding, which can be seen as a challenge for medical teaching. Hence, the purpose of this study was to analyse what kind of initial mental models students have about the CCVS and how these models change after a course. Further, we were interested in how medical students evaluate the role of problem-based learning (PBL)-enriched conventional instruction in their learning of the CCVS. Pre- and posttests consisting of a drawing task were conducted with 60 Finnish medical students. Additionally, problem-based learning and course evaluation questionnaires were administered. Results show that one-third of the students had misconceptions such as single-loop concepts in understanding the CCVS before the course. Although the instruction seems to support conceptual change, 10% of the students did not reach a scientific model. In their evaluations of the learning environment, the students appreciated working in small groups in addition to lectures. Sixty-five percent of the students considered PBL an effective learning method, whereas the rest of the students found it ineffective. In sum, although most of the first-year medical students reached an adequate representation of the central cardiovascular system, too many seem to have resistant misconceptions. Hence, in developing learning environments that support students' conceptual change in the medical domain, students' prior knowledge and perceptions of learning environments need to be taken into account.