This study assessed challenges faced by researchers with the informed consent process (ICP). In-depth interviews were used to explore challenges encountered by Investigators, Research assistants, Institutional Review Board members and other stakeholders. An electronic questionnaire was also distributed, consisting of Likert-scale responses to questions on adherence to the ICP, which were derived from the Helsinki Declaration and an informed consent checklist of the US Department of Health and Human Research (HSS). Responses were weighted numerically and scores calculated for each participant. The median score of the level of adherence to the informed consent process was 93%. Most of the respondents (60%) cited the lack of time for the ICP to be a challenge, with 65% indicating a lengthy consent document to be the main challenge with the informed consent document. Challenges with language and communication were the dominant theme among informants. Despite the high adherence of Ghanaian researchers and research assistants to the ICP, challenges are still prevalent, requiring diligent and continuous efforts in research implementation.