ObjectivesHow advance care planning (ACP) is conceptualised in Australia including when, where and how ACP is best initiated, is unclear. It has been suggested that healthcare delivered in general practice provides an optimal setting for initiation of ACP discussions but uptake remains low. This systematic review and critical interpretive synthesis sought to answer two questions: (1) What are the barriers and enablers to uptake of ACP in general practice? (2) What initiatives have been used to increase uptake of ACP in general practice?DesignA systematic review and critical interpretive synthesis of the peer-reviewed literature was undertaken. A socioecological framework was used to interpret and map the literature across four contextual levels of influence including individual, interpersonal, provider and system levels within a general practice setting.SettingPrimary care general practice settingsData sourcesSearches were undertaken from inception to July 2019 across Ovid Medline, Cumulative Index to Nursing and Allied Health Literature, Scopus, ProQuest and Cochrane Library of systematic reviews.ResultsThe search yielded 4883 non-duplicate studies which were reduced to 54 studies for synthesis. Year of publication ranged from 1991 to 2019 and represented research from nine countries. Review findings identified a diverse and disaggregated body of ACP literature describing barriers and enablers to ACP in general practice, and interventions testing single or multiple mechanisms to improve ACP generally without explicit consideration for level of influence. There was a lack of cohesive guidance in shaping effective ACP interventions and some early indications of structured approaches emerging.ConclusionFindings from this review present an opportunity to strategically apply the ACP research evidence across targeted levels of influence, and with an understanding of mediators and moderators to inform the design of new and enhanced ACP models of care in general practice.PROSPERO registration numberCRD42018088838