We developed measures of benefits and burdens of research participation in cancer clinical trials using a sequential mixed methods design with a qualitative ( n = 32) and quantitative sample ( n = 110) of cancer clinical trial participants. Benefit-burden items (22 for benefits, 23 for burdens) were subsequently developed and assessed through cognitive interviewing for content, clarity, and meaning. Preliminary psychometric analyses support the internal consistency reliability and construct validity of Benefit (α = .90) and Burden (α = .87) research participation scales. Item response theory models supported the discrimination ability of the items on the scales. Participants who had thoughts of dropping out had lower Benefit scale scores ( p < .001) and higher Burden scores ( p < .001) than those who had no thoughts of dropping out, supporting construct validity. With further psychometric testing, the scale can be used to develop appropriate interventions to address recruitment and retention of human participants in clinical research.