Background Contralateral prophylactic mastectomy (cpm) in women with known unilateral breast cancer (bca) has been increasing despite the lack of supportive evidence. The purpose of the present study was to identify the determinants of cpm in women with unilateral bca.Methods This qualitative descriptive study used semi-structured interviews informed by the Theoretical Domains Framework. We interviewed 74 key informants (surgical oncologists, plastic surgeons, medical oncologists, radiation oncologists, nurses, women with bca) across Canada. Interviews were analyzed using thematic analysis and an analysis for shared and discipline-specific beliefs.Results In total, 58 factors influencing the use of cpm were identified: 26 factors shared by various health care professional groups, 15 discipline-specific factors (identified by a single health care professional group), and 17 factors shared by women with unilateral bca. Health care professionals identified more factors discouraging the use of cpm (n = 26) than encouraging its use (n = 15); women with bca identified more factors encouraging use of cpm (n = 12) than discouraging its use (n = 5). The factor most commonly identified by health care professionals that encouraged cpm was lack of awareness of existing evidence or guidelines for the appropriate use of cpm (n = 44, 75%). For women with bca, the factor most likely influencing their decision for cpm was wanting a better esthetic outcome (n = 14, 93%).Conclusions Multiple factors discouraging and encouraging the use of cpm in unilateral bca were identified. Those factors identify potential individual, team, organization, and system targets for behaviour change interventions to reduce cpm.