A practical, reliable, and valid instrument is needed to measure the impact of the learning environment on medical students' well-being and educational experience and to meet medical school accreditation requirements. From 2012 to 2015, medical students were surveyed at the end of their first, second, and third year of studies at four medical schools. The survey assessed students' perceptions of the following nine dimensions of the school culture: vitality, self-efficacy, institutional support, relationships/inclusion, values alignment, ethical/moral distress, work-life integration, gender equity, and ethnic minority equity. The internal reliability of each of the nine dimensions was measured. Construct validity was evaluated by assessing relationships predicted by our conceptual model and prior research. Assessment was made of whether the measurements were sensitive to differences over time and across institutions. Six hundred and eighty-six students completed the survey (49% women; 9% underrepresented minorities), with a response rate of 89% (range over the student cohorts 72-100%). Internal consistency of each dimension was high (Cronbach's α 0.71-0.86). The instrument was able to detect significant differences in the learning environment across institutions and over time. Construct validity was supported by demonstrating several relationships predicted by our conceptual model. The C-Change Medical Student Survey is a practical, reliable, and valid instrument for assessing the learning environment of medical students. Because it is sensitive to changes over time and differences across institution, results could potentially be used to facilitate and monitor improvements in the learning environment of medical students.