A major goal of higher education is to create an environment conducive to quality student learning. Medical practitioners should possess a sound knowledge of anatomy to enable them to diagnose patients accurately and treat them successfully. Studies have reported a decline in the knowledge of anatomy acquired by students, recent medical graduates and newly qualified medical trainees. Various interdependent factors--individual, organisational, environmental, and relating to academic programmes--have been reported to influence first-year students' academic performance. The study reported on aimed to obtain the perspectives of first-year medical students at a South African university on the effect of individual, organisational, environmental and academic programme factors on their academic performance in anatomical sciences. The research was designed as a descriptive, exploratory study that used a self-administered questionnaire with both quantitative and qualitative components. The questionnaires were administered manually to 133 first-year medical students to obtain their perspectives on the effect of selected personal, institution/faculty, course/module and curriculum factors on their academic performance. Factors that had a positive effect on their academic performance were personal motivation, academic ability, intelligence, academic environment, the outcomes-based curriculum, and the organisation and layout of the module; while factors that had a negative effect were workload, load of independent study, difficulty of content, difficulty of language used in study material, and assessment. The study found that certain factors had both a positive and a negative effect on academic performance. The results can be used to address problematic areas of the module to improve academic performance.