Introduction: An extensive research in the medical education has brought a paradigm shift from a routine traditional lecturing to new innovative methods of teaching which are more student-centered. Use of crossword puzzles provides a simple and creative way to incorporate active learning in human anatomy, a subject which introduces the students to core knowledge of human body with newer terms and concepts which are totally different from their pre-existing knowledge. Aim: The aim of the study is to evaluate the usefulness of crossword puzzles as a learning tool at the level of the undergraduate medical curriculum. Objectives: To evaluate the student’s perceptions regarding the usefulness of crosswords as an effective mode to reinforce the essential concepts and vocabulary, and to design, and evaluate the use of crossword puzzles as an educational tool in anatomy teaching and learning. Materials and methods: The research study was carried out at Shadan Institute of Medical Sciences, Hyderabad, India. The study sample included 150 students of 1st-year MBBS of batch 2015-2016, which were divided into 25 groups. These groups were given an exercise of total 8 crossword puzzles, one each after the completion of all sessions in each region of the human anatomy. Results: Majority of the students agreed that the use of the crossword was an innovative method of learning, whereas few students suggested that more time should be allotted and these activities should be given individually rather than in small groups. Conclusion: Using crossword puzzles provides an opportunity for the students to develop approaches to critical learning for understanding human anatomy. Students perceive the crossword puzzles as an active learning exercise.