Importance Use of percutaneous cholecystostomy (PC) has increased over the past 20 years without consensus regarding indications and management. Objective To identify indicators for PC, clarify the management of a PC tube (PCT), and suggest the timing of further interventions. Evidence Review A systematic review was conducted to identify studies examining PC. Five databases were selected and searched from inception to December 31, 2024: PubMed, Embase, Cochrane, ICTRP, and ClinicalTrials.gov. Inclusion criteria were prior systematic reviews and meta-analyses published within the last 5 years, randomized clinical trials, prospective cohort studies, retrospective cohorts, cross-sectional studies, and case-control studies with multivariate analyses. Findings Of 3774 publications identified, 69 studies met the inclusion criteria. There were 5 randomized clinical trials, 2 prospective cohort analyses, 40 retrospective cohort analyses, 1 case-control study, 12 cross-sectional studies, 3 systematic reviews, and 6 meta-analyses. PC was outperformed by cholecystectomy and offered no apparent benefit compared to antibiotic-only management (AOM) except among patients with concomitant sepsis. Interval cholecystectomy (IC) following PC was associated with better outcomes compared to a definitive PC. Factors associated with failure to undergo IC include congestive heart failure (CHF) and chronic liver disease (CLD). IC within 8 weeks and beyond 13 weeks after PC was associated with increased complications. Removal of PC before IC was associated with reduced complications but an increase in the likelihood of undergoing emergency IC. A PCT clamp trial was a better test than tube cholangiogram for PCT removal. Conclusion and Relevance PC should only be considered among poor surgical candidates unable to undergo immediate cholecystectomy. Indications for PC include cholecystitis sepsis or AOM failure. PC should be approached as a bridging therapy to IC with careful consideration among patients with CHF and CLD. PC removal before IC should be guided by a successful clamping trial to reduce complications and interim recurrence. IC should be performed 8 to 13 weeks after PC.