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In recent years, student learning outcomes have become an important aspect when examining the effectiveness of higher education. Many factors, including student and institutional characteristics may need to be considered to reach a fair and accurate interpretation learning outcomes assessment. In this study, we investigated the relationship between major-related outcomes test scores and characteristics of students, institutions, and cohorts with nearly half a million of college students, in 15 majors, from over 1000 schools, between 2005 and 2011. Results revealed that learning outcomes test scores were associated with student and institutional characteristics, and varied across cohort years, which all should be carefully examined when using outcomes assessment results to make comparisons, inferences or decisions on the effectiveness of higher education.