Background Healthcare organisations have legal and ethical duties to reduce inequalities in access to healthcare services and related outcomes. However, lesbian, gay, bisexual and/or transgender (LGBT+) people continue to experience and anticipate discrimination in health and social care. Skilled communication is vital for quality person-centred care, but there is inconsistent provision of evidence-based clinician education on health needs and experiences of LGBT+ people to support this. This study aimed to identify key stakeholders' experiences, preferences and best practices for communication regarding sexual orientation, gender identity and gender history in order to reduce inequalities in healthcare. Methods Semistructured qualitative interviews with LGBT+ patients with serious illness, significant others and clinicians, recruited via UK-wide LGBT+ groups, two hospitals and one hospice in England. We analysed the interview data using reflexive thematic analysis. Results 74 stakeholders participated: 34 LGBT+ patients with serious illness, 13 significant others and 27 multiprofessional clinicians. Participants described key communication strategies to promote inclusive practice across three domains: (1) 'Creating positive first impressions and building rapport' were central to relationship building and enacted through routine use of inclusive language, avoiding potentially negative non-verbal signals and echoing terminology used by patients and caregivers; (2) 'Enhancing care by actively exploring and explaining the relevance of sexual orientation and gender identity', participants described the benefits of clinicians initiating these discussions, pursuing topics guided by the patient's response or expressed preferences for disclosure. Active involvement of significant others was encouraged to demonstrate recognition of the relationship; these individual level actions are underpinned by a foundation of (3) 'visible and consistent LGBT+ inclusiveness in care systems'. Although participants expressed hesitance talking about LGBT+ identities with individuals from some sociocultural and religious backgrounds, there was widespread support for institutions to adopt a standardised, LGBT+ inclusive, visibly supportive approach. Conclusions Person-centred care can be enhanced by incorporating discussions about sexual orientation and gender identity into routine clinical practice. Inclusive language and sensitive exploration of relationships and identities are core activities. Institutions need to support clinicians through provision of adequate training, resources, inclusive monitoring systems, policies and structures. Ten inclusive communication recommendations are made based on the data.