Randomized clinical trials (RCTs) are an essential method of evaluating health care interventions and a cornerstone for evidence-based health care. However, RCTs have become increasingly complex and costly, which is particularly challenging for independent investigator-initiated clinical trials (IICTs). IICTs have an essential role in clinical research, and it is important that efforts are made to ensure IICTs are adequately funded and are conducted cost-effectively.To examine the practices and attitudes of Swiss stakeholders regarding IICT funding acquisition and cost management.For this qualitative study, interviews were conducted in Switzerland between February and August 2020. The purposive sample comprised 48 stakeholders from 4 different groups: primary investigators (n = 27), funders and sponsors (n = 9), clinical trial support organizations (n = 6), and ethics committee members (n = 6).Practices and attitudes of stakeholders regarding IICT funding acquisition and cost management were assessed using individual semistructured qualitative interviews. Interviews were analyzed using conventional content analysis.After interviews with 48 IICT stakeholders (75\% male presenting), these participants identified a systemic problem of IICTs being underfunded, which can lead to compromises being made regarding the quality and conduct of IICTs. Participants identified 2 overarching and interconnected groups of reasons why IICTs in Switzerland are regularly underfunded. First, it was reported that IICT budget estimations are often inaccurate because of poor planning and preparation, unforeseeable events, investigators intentionally underestimating budgets, and limited budget assessment and oversight. Second, with the exception of a specific IICT funding program by the Swiss National Science Foundation, it was reported that limited funding sources and unrealistic expectation of funders led to underlying challenges in getting IICTs fully funded. A number of measures that could help reduce the underfunding of IICTs were identified, including improving the support of investigators and IICTs, strengthening networking and guidance, harmonizing and simplifying bureaucracy, and increasing public funding of IICTs.This study highlights the inadequate expertise of Swiss stakeholders to correctly, systematically, and reproducibly calculate RCT budgets and the need for transparency on trial costs as well as training in budgeting practices. Limited financial resources for academic clinical research and issues regarding the professional planning and conduct of IICTs are persistent issues that many other countries also face.