Background The Tokyo Guidelines recommend initial cholecystostomy tube drainage, antibiotics, and delayed cholecystectomy in patients with grade III cholecystitis. Study Design We used Medicare data (1996 to 2010) to identify patients 66 years and older who were admitted with grade III acute cholecystitis. We evaluated adherence to the Tokyo Guidelines and compared mortality, readmission, and complication rates with and without cholecystostomy tube placement in a propensity-matched (1:3) cohort of patients with grade III cholecystitis. Results There were 8,818 patients admitted with grade III cholecystitis; 565 patients (6.4%) had a cholecystostomy tube placed. Cholecystostomy tube placement increased from 3.9% to 9.7% during the study period. Compared with 1,689 propensity-matched controls, patients with cholecystostomy tube placement had higher 30-day (hazard ratio HR = 1.26; 95% CI 1.05 to 1.50), 90-day (HR = 1.26; 95% CI 1.08 to 1.46), and 2-year mortality (HR = 1.19; 95% CI 1.04 to 1.36) and were less likely to undergo cholecystectomy in the 2 years after initial hospitalization (33.4% vs 64.4%; HR = 0.26; 95% CI 0.21 to 0.31). Readmissions were also higher at 30 days (HR = 2.93; 95% CI 2.12 to 4.05), 90 days (HR = 3.48; 95% CI 2.60 to 4.64), and 2 years (HR = 3.08; 95% CI 2.87 to 4.90). Conclusions Since the introduction of the Tokyo Guidelines (2007), use of cholecystostomy tubes in patients with grade III cholecystitis has increased, but the majority of patients do not get cholecystostomy tube drainage as first-line therapy. Cholecystostomy tube placement was associated with lower rates of definitive treatment with cholecystectomy, higher mortality, and higher readmission rates. These data suggest a need for additional evaluation and refinement of the Tokyo Guidelines.