Traffic incidents, often known as nonrecurring events, impose enormous economic and social costs. Compared with short-duration incidents, large-scale incidents can substantially disrupt traffic flow by blocking lanes on highways for long periods. A careful examination of large-scale traffic incidents and associated factors can assist with actionable largescale incident management strategies. For such an analysis, a unique and comprehensive 5-year incident database on East Tennessee roadways was assembled to conduct an in-depth investigation of large-scale incidents, especially focusing on operational responses, that is, response and on-scene times by various agencies. Incidents longer than 120 min andblocking at least one lane were considered large scale; the database contained 890 incidents, which was about 0.69% of all reported incidents. Rigorous fixed-and random-parameter, hazard-based duration models were estimated to account for the possibility of unobserved heterogeneity in large-scale incidents. The modeling results reveal significant heterogeneity in associations between operational responses and large-scale incident durations. A 30-min increase in response time for the first, second, and third (or more) highway response units translated to a 2.8%, 1.6%, and 4.2% increase in large-scale incident durations, respectively. In addition, longer response times for towing and highway patrol were significantly associated with longer incident durations. Given large-scale incidents, associated factors included vehicle fire, unscheduled roadwork, weekdays, afternoon peaks, and traffic volume. Notably, the associations were heterogeneous; that is, the direction could be positive in some cases and negative in others. Practical implications of the results for large-scale incident management are discussed.