The fire started late in the evening, and it moved fast. The Comayagua penitentiary had no smoke detectors, no sprinkler system, no fire alarm pull stations, and no manual fire extinguishers. Because the facility held more than 800 inmates in a space designed for fewer than 400, prisoners slept in bunk beds stacked four high. They had fashioned their own privacy by surrounding their bunks with wood panels, bedsheets, and towels. The mattresses were thin cloth filled with polyurethane foam. Every surface was fuel. One prisoner later described the desperate moments after the fire was discovered: calls for help went out immediately, but for a terrible stretch of time, nobody responded. "After a few minutes, which seemed like an eternity, a guard appeared with keys and let us out." Others were not as fortunate. Firefighters reported that around 100 inmates burned to death or suffocated in their locked cells because keys to release them could not be found.

The death toll, 361 people, was so large that the chief of forensic medicine estimated it would take at least three months to identify the victims, primarily through DNA samples. Dozens of the dead had been burned beyond recognition. According to The Guardian, most of the prisoners killed had not yet been convicted. They were awaiting trial in a justice system overwhelmed by its own caseload, held in a facility overwhelmed by its own population. The U.S. State Department had already documented the conditions these people endured: malnutrition, overcrowding, and unsanitary facilities. Honduras's own security minister had described the nation's prisons in 2010 as "universities of crime," an acknowledgment of systemic failure that did nothing to prevent what happened two years later. Around 30 prisoners with severe burns were transported to Tegucigalpa for specialist treatment. Outside the prison walls, families gathered to learn whether their relatives were alive, and when answers came too slowly, some attempted to storm the facility. Police used tear gas to push them back.

The fire exposed what human rights observers had been saying for years. Ron W. Nikkel, president of Prison Fellowship International, said the Comayagua prison was one of the worst he had ever seen when he visited in 2005. Jose Miguel Vivanco of Human Rights Watch called the tragedy "the result of prison conditions that are symptomatic of the country's larger public security crisis." Honduras's prisons were designed for roughly 6,000 inmates nationwide; at the time of the fire, they held more than 12,000. The Comayagua facility alone was at more than double its intended capacity. The U.S. Bureau of Alcohol, Tobacco, Firearms and Explosives sent investigators at the Honduran government's request. Initial statements from a prison official attributed the fire to arson by an inmate; that claim was later retracted, with prison authorities blaming an electrical fault instead. The ATF investigation concluded the fire was accidental, a finding that the victims' families disputed.

President Porfirio Lobo Sosa promised a "full and transparent" investigation into what he called an "unacceptable" tragedy. International aid arrived: Mexico's President Felipe Calderon pledged medics and supplies, Chile sent fourteen forensic experts, and Israel's ambassador offered to facilitate construction of four new prisons with modern safety systems. Soto Cano Air Base, the U.S. military installation just fifteen minutes from the prison, provided immediate American and Honduran aid. But the harder questions had no easy answers. How does a country reform a prison system that has twice the inmates it was built to hold? How do you prevent the next fire in a facility where fire prevention equipment was never installed? The 361 people who died in Comayagua were not abstractions. They were someone's children, parents, siblings. Many were awaiting their day in court, a day that never came. Their deaths demand to be remembered not as a statistic but as a failure, systemic and specific, that cost real human lives.