Background: The HALT Polycystic Kidney Disease Trials Network consisted of two randomized, double blind, placebo-controlled trials among patients with autosomal dominant polycystic kidney disease. The trials involved 5–8 years of participant follow-up with interventions in blood pressure and antihypertensive therapy. We provide a framework for designing and implementing closeout near the end of a trial while ensuring patient safety and maintaining scientific rigor and study morale. Methods: We discuss issues and resolutions for determining the last visit, tapering medications, and unblinding of participants to study allocation and results. We also discuss closure of clinical sites and Data Coordinating Center responsibilities to ensure timely release of study results and meeting the requirements of regulatory and funding authorities. Results: Just over 90% of full participants had a 6-month study visit prior to their last visit preparing them for trial closeout. Nearly all patients wanted notification of study results (99%) and treatment allocation (99%). All participants were safely tapered off study and open label blood pressure medications. Within 6 months, the trials were closed, primary papers published, and 805 letters distributed to participants with results and allocation. DCC obligations for data repository and clinicaltrials.gov reporting were completed within 12 months of the last study visit. Conclusions: Closeout of our trials involved years of planning and significant human and financial resources. We provide questions for investigators to consider when planning closeout of their trials with focus on (1) patient safety (2) dissemination of study results and (3) compliance with regulatory and funding responsibilities.