Background Management of gallbladder wall calcifications has been controversial for many decades. Although the traditionally perceived strong association with gallbladder cancer mandated prophylactic cholecystectomy, newer evidence suggests a much lesser association and might indicate an observational approach. Study Design A retrospective cohort study of 113 patients with gallbladder wall calcifications diagnosed between 2004 and 2016 at a single institution was conducted. Radiographic re-review identified patients with definitive (n = 70) and highly probable (n = 43) gallbladder wall calcifications. Patients were categorized according to their designated treatment plan. Results In the observation group (n = 90), delayed cholecystectomy for gallbladder-related symptoms was necessary in 4 patients (4%). None of the patients in this group were diagnosed with a gallbladder malignancy during a mean of 3.2 ± 3.2 years follow-up. In the operative group (n = 23), peri-operative complications occurred in 13%, and gallbladder malignancy was found in 2 patients. In comparison, although patients in the observation group were older and had more comorbidities, the rate of adverse events was not significantly different (4% vs 13%; p = 0.15) with an overall low risk for potentially life-threatening complications to the patient when observed clinically. Conclusions For management of gallbladder wall calcifications, observation appears to provide no significant difference in adverse events, including the risk of gallbladder malignancy developing, compared with an operative approach. Although there is a need for intervention in the presence of symptoms and findings suggestive of malignancy, prophylactic cholecystectomy should be avoided in patients with limited life expectancy and significant comorbidities.