Introduction: Clinical trial is an extensive and demanding process, which takes approximatelyrn10 to 15 years. Clinical trials require the active engagement of human subjects. Recruitment andrnretention of participants are two major challenges in conducting clinical trials. Poor recruitmentrnand retention of participants in clinical trials can lead to major delays in the development of newrnproducts and interventions. This can also cause significant problems in the study validity as theyrncould reduce the statistical power resulting in poor generalizability of the study. rnObjective: This study is aimed to identify potential challenges and strategies for enhancingrnrecruitment and retention of participants in clinical trials in Ethiopia. rnMethod: A qualitative methodology with a phenomenological approach employed. Semistructuredrnrninterviews were conducted face to face and through telephone. Interviewees werernpurposively selected from five candidate study sites which are Armauer Hansen Research Institute,rnZewditu Memorial Hospital, University of Gondar, Jimma University, and Addis AbabarnUniversity. These sites were chosen primarily because most clinical trials conducted in andrnpotential clinical investigator candidates were employed and affiliated there. Investigators, clinicalrncoordinators, physicians, nurses, and participants involved in clinical trials were the studyrnrespondents. The sample size was determined using the criterion of informational redundancy. Ofrn22 potential respondents approached, 19 consented to the interview. An open-ended topic guidernwas developed to facilitate in-depth interviews with respondents with sufficient freedom torndescribe their experiences and perspectives that they deemed relevant to the research questions.rnInterviews were audio-recorded with consent. Transcriptions were entered into Open Code andrncoded. Data were analyzed using thematic analysis. rnResult: Nine of the respondents (47.4%) were females. Respondents were involved as principalrninvestigators (n=5), trial coordinators (n=7), nurses (n=2), physicians (n=2) and trial participantsrn(n=3). Thematic analysis resulted in a generation of 3 main themes and 10 sub-themes. Clinicalrntrial team factors (communication and system-related), participantsâ€™ factors (communication andrninterest related), and study factors (complexity of the study and cost-related) were listed asrnchallenges for recruitment and retention of trial participants. Additionally, four subthemes arernmentioned under the three themes as a strategy for recruitment and retention of trial participants,rnsuch as promoting clinical trials, improving communication skills, refining the clinical trial setting system, and having a good estimation of cost. Potential challenges and strategies for recruitmentrnand retention of participants in clinical trials were identified under each sub-themes. Poorrncommunication skills, mistreating participants, and lack of knowledge about existing trials arernconsidered to be clinical trial team factors. Also, misconceptions about the trial, low-levelrneducation, lack of social support, and participantsâ€™ moves around were revealed to be an importantrnchallenge among trial participantsâ€™ factors. Also study factors such as long questionnaires andrnassessment, stringent eligibility criteria, frequent appointment, and extra, and inconvenientrnprocedures. However, a wide range of strategies was identified such as increasing awareness,rnchoosing an appropriate trial site, provisions of training, reimbursement and compassionaternrespectful care, and establishing an efficient tracking system may be the most importantrninterventions to improve recruitment and retention of trial participants. rnConclusions: Poor knowledge about research, and complexity of trials were the greatestrnchallenges for low recruitment and retention. Interventions to improve knowledge and provisionsrnof training to the clinical trial team and having compassionate respectful care, providingrncompensation, increasing awareness in the community are important strategies to consider whenrndesigning and planning recruitment and retention plan.