Background The effectiveness of complex interventions, as well as their success in reaching relevant populations, is critically influenced by their implementation in a given context. Current conceptual frameworks often fail to address context and implementation in an integrated way and, where addressed, they tend to focus on organisational context and are mostly concerned with specific health fields. Our objective was to develop a framework to facilitate the structured and comprehensive conceptualisation and assessment of context and implementation of complex interventions. Methods The Context and Implementation of Complex Interventions (CICI) framework was developed in an iterative manner and underwent extensive application. An initial framework based on a scoping review was tested in rapid assessments, revealing inconsistencies with respect to the underlying concepts. Thus, pragmatic utility concept analysis was undertaken to advance the concepts of context and implementation. Based on these findings, the framework was revised and applied in several systematic reviews, one health technology assessment (HTA) and one applicability assessment of very different complex interventions. Lessons learnt from these applications and from peer review were incorporated, resulting in the CICI framework. Results The CICI framework comprises three dimensions—context, implementation and setting—which interact with one another and with the intervention dimension. Context comprises seven domains (i.e., geographical, epidemiological, socio-cultural, socio-economic, ethical, legal, political); implementation consists of five domains (i.e., implementation theory, process, strategies, agents and outcomes); setting refers to the specific physical location, in which the intervention is put into practise. The intervention and the way it is implemented in a given setting and context can occur on a micro, meso and macro level. Tools to operationalise the framework comprise a checklist, data extraction tools for qualitative and quantitative reviews and a consultation guide for applicability assessments. Conclusions The CICI framework addresses and graphically presents context, implementation and setting in an integrated way. It aims at simplifying and structuring complexity in order to advance our understanding of whether and how interventions work. The framework can be applied in systematic reviews and HTA as well as primary research and facilitate communication among teams of researchers and with various stakeholders. Electronic supplementary material The online version of this article (doi:10.1186/s13012-017-0552-5) contains supplementary material, which is available to authorized users.