Medical Education 2012: 46:678688 Context Medical schools wish to better understand why some students excel academically and others have difficulty in passing medical courses. Components of self-regulated learning (SRL), such as motivational beliefs and learning strategies, as well as participation in scheduled learning activities, have been found to relate to student performance. Although participation may be a form of SRL, little is known about the relationships among motivational beliefs, learning strategies, participation and medical school performance. Objectives This study aimed to test and cross-validate a hypothesised model of relationships among motivational beliefs (value and self-efficacy), learning strategies (deep learning and resource management), participation (lecture attendance, skills training attendance and completion of optional study assignments) and Year 1 performance at medical school. Methods Year 1 medical students in the cohorts of 2008 (n = 303) and 2009 (n = 369) completed a questionnaire on motivational beliefs and learning strategies (sourced from the Motivated Strategies for Learning Questionnaire) and participation. Year 1 performance was operationalised as students average Year 1 course examination grades. Structural equation modelling was used to analyse the data. Results Participation and self-efficacy beliefs were positively associated with Year 1 performance (beta = 0.78 and beta = 0.19, respectively). Deep learning strategies were negatively associated with Year 1 performance (beta = - 0.31), but positively related to resource management strategies (beta = 0.77), which, in turn, were positively related to participation (beta = 0.79). Value beliefs were positively related to deep learning strategies only (beta = 0.71). The overall structural model for the 2008 cohort accounted for 47% of the variance in Year 1 grade point average and was cross-validated in the 2009 cohort. Conclusions This study suggests that participation mediates the relationships between motivation and learning strategies, and medical school performance. However, participation and self-efficacy beliefs also made unique contributions towards performance. Encouraging participation and strengthening self-efficacy may help to enhance medical student performance.