Background: Problem-based learning (PBL) as a teaching strategy has recently become quite widespread in especially chemistry classes. Research has found that students, from elementary through college, have many alternative conceptions regarding "enthalpy changes in systems." Although there are several studies focused on identifying student alternative conceptions and misunderstandings of this subject, studies on preventing the formation of these alternative conceptions are limited. Purpose: The aim of this study was to improve the learning achievements of students and to investigate the effects of PBL and thereby prevent the formation of alternative conceptions with respect to the teaching of the chemistry lesson, "enthalpy changes in systems." Sample: The population of the study consisted of 41 students from 2 11th-grade high school classes in Izmir, Turkey. Design and methods: As a pre- and post-test quasi-experimental design was used for the study, one of the two classes was randomly assigned as the experimental group, and the other was used as the control group. In teaching the subject, the developed material was taught by the same teacher who applied PBL in the experimental group and traditional teaching methods in the control group. At the end of the teaching units, a post-test was administered to determine the level of student learning and achievement. Results It was concluded from the obtained results that the average success of the experimental group was significantly higher than that of the control group and that the experimental group had significantly fewer alternative conceptions, conceptual difficulties, and lack of knowledge than did the control group. Conclusions PBL is an effective active learning approach that enhances achievement and prevents the formation of alternative conceptions, conceptual difficulties and lack of knowledge among 11th-grade students with respect to "enthalpy changes in systems." The results suggest that if PBL were more widely applied in classes, students would acquire the skills necessary to be successful in life.