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There have been several major wars starting from the invasion of the Andals to Aegon's Conquest, Faith Uprising, Dance of the Dragons, Daeron the First's invasion of Dorne, Blackfyre rebellions, War of the Ninepenny Kings, Robert's Rebellion and The War of the Five Kings.(LIST NOT EXCLUSIVE)

Which war had the most devastating effect on human life in terms of casualties?

Not interested in any fights against White Walkers.

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There's no explicit information available on death toll of each war.

But if we had to speculate, I think Dance of the Dragons would be the most destructive in both economic cost and human life cost. Dragons are the most deadly weapon of war which can cause mass destruction. And Dance of the Dragons was the only time the largest number of dragons Westeros had ever seen were put to use. We do not know exact number of people who died but we can make a safe guess judging by:

  1. Free use of dragons
  2. Prince Aemond's unrestricted aerial warfare
  3. Near extinction of the Royal House
  4. The highest number of Widows and babies ruling the lands of their fathers. Imagine how bad did the common people had it, if such was the state of aristocracy
  5. The extent of war which had engulfed all the Kingdoms except Iron Islands.
  6. Major towns such as Tumbleton, Spice Town that were utterly destroyed and never restored

That DoD was indeed the worst war the Seven Kingdoms ever saw. We know that nobles and knights are less likely to die than a common peasant and Royal family members even less than lesser nobles. Yet in this war, it was recorded that such an astounding number of nobles died that many lands including the great castles such as High Garden (Although Lord Tyrell had died naturally before the War), Storm's End, and Casterly Rock were inherited by toddlers and their mothers the widows were ruling as regents. The commonfolk suffered so much, that to overcome the sudden shortage of men, Northmen settled the lands of Trident and Widowfairs were held so that Widows and the Northmen, who'd come riding south in hopes of dying and giving their kin a better chance in surviving winter, could be wed en masse. The court fool Mushroom made a jape of it, "A wolf for every widow". The Royal House itself had been reduced to the royal Persons of King Aegon III, his sisters Baela and Rhaena and his Queen Jaehaera. And worst of all for Targaryens, nearly all the Dragons had died.

When we look at the other wars:

  • Aegon's Conquest: The Conqueror didn't shed blood unnecessarily. He welcomed all those who yielded to his camp with open arms, affirmed the rights of his new subjects and tried to limit the casualties as much as he could. Only a handful of times were the Dragons put to use, once at Harrenhal (Balerion), Once at Sea (Vhagar) and once at the Last Storm (Meraxes). And only one time did the Targaryens use all three dragons at once; The Field of Fire. Dornish war was a different story however, After Queen Rhaenys was killed the battles turned to butchery.

  • Faith Uprising: The Crown always had the upper hand and even Maegor the Cruel rarely used his dragon. By the mid of it, Faith had been forced to fight the war from the shadows and Royal Armies were limited to counter-insurgency.

  • Daeron's first invasion: Surprisingly effective and low cost. All dragons had died before it. Dornish lords were forced into swift submission.

  • Blackfyre Rebellions: Only the first Blackfyre Rebellion could rival the Dance in scope and intensity. But even in that one, the Death toll seems lower given that male population didn't decline as steeply as it did in the Dance and the Royal House along with nobles for the most part survived. The other Blackfyre rebellions were nothing more than nuisances.

  • Robert's Rebellion: Definitely nowhere as brutal as the Dance. The Rebels won quick victories at Gulltown, Battle of Bells and Trident. And King's Landing fell quickly along with Dragonstone.

  • War of the Five Kings: Still on going but we could assume that if any war could rival the Dance, it would be this one. We will have to wait till its conclusion.

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