ImportanceExtreme risk protection orders (ERPOs) temporarily bar individuals adjudicated as being at risk of violence (including suicide) from buying or possessing firearms. In protest, many US jurisdictions have declared themselves “Second Amendment sanctuaries” (2A sanctuaries). Many 2A sanctuaries continue to use ERPOs in low numbers, suggesting a poorly defined risk threshold at which they are acceptable.ObjectiveTo characterize circumstances under which ERPOs are used in 2A sanctuaries, highlighting their most broadly acceptable applications.Design, Setting, and ParticipantsThis cross-sectional study of civil court documents analyzed petitions for ERPOs filed in Colorado from January 2020 to December 2022. All petitions during the study period were included following de-duplication. These include petitions filed by law enforcement and family members against adults allegedly at risk of firearm violence across the state. Data were analyzed on a rolling basis between January 2020 and June 2023.ExposureERPO petition filed in Colorado.Main Outcomes and MeasuresSeventy-seven data elements defined a priori were abstracted from all petitions and case files, including respondent demographics, petitioner types (family or law enforcement), types of threats (self, other, mass violence, combination), violence risk factors, and case outcomes (granted, denied).ResultsOf a total 338 ERPOs filed in Colorado, 126 (37.3%) occurred in 2A sanctuaries. Sixty-one of these 2A petitions were granted emergency orders, and 40 were full 1-year ERPOs after a hearing. Forty ERPOs (31.7%) were petitioned for by law enforcement. Petitions in non-2A counties were more likely to have been filed by law enforcement (138 of 227 [64.9%] vs 40 of 126 [31.7%]; P < .001) and to have had an emergency order granted (177 of 227 [78.0%] vs 61 of 126 [48.4%]; P < .001) than in 2A sanctuaries. Qualitative analysis of cases in 2A sanctuaries revealed common aggravating risk characteristics, including respondents experiencing hallucinations, histories of police interaction, and substance misuse. ERPOs have been granted in 2A sanctuaries against individuals threatening all forms of violence we abstracted for (themselves, others, and mass violence).Conclusions and RelevanceIn this examination of ERPO petitions across Colorado, more than a third of filings occurred in 2A sanctuaries. Nonetheless, law enforcement represent proportionately fewer petitions in these areas, and petitions are less likely to be granted. Serious mental illness, substance misuse, and prior interactions with law enforcement featured prominently in 2A sanctuary petitions. These case circumstances highlight dangerous situations in which ERPOs are an acceptable risk-prevention tool, even in areas politically predisposed to opposing them.