In 1572, following several unsuccessful attempts at brokering peace, Charles arranged the marriage of his sister Margaret to Henry of Navarre, a major Protestant nobleman in the line of succession to the French throne, in a last desperate bid to reconcile his people.

Facing popular hostility against this policy of appeasement and at the instigation of his mother Catherine de' Medici, Charles oversaw the massacre of numerous Huguenot leaders who gathered in Paris for the royal wedding, though his direct involvement is still debated.

However, the incident haunted Charles for the rest of his life, and historians suspect that it caused his physical and mental health to deteriorate over the next two years.

[11] Antoine of Bourbon, himself in line to the French throne and husband to Queen Jeanne III of Navarre, was appointed Lieutenant-General of France.

[13][14] The regent Catherine tried to foster reconciliation at the Colloquy at Poissy and, after that failed, made several concessions to the Huguenots in the Edict of Saint-Germain in January 1562.

[15] Nonetheless, the Massacre of Vassy, perpetrated on 1 March 1562, when the Duke of Guise and his troops attacked and killed or wounded over 100 Huguenot worshipers and citizens, brought France spiralling towards civil war.

Louis of Bourbon, Prince of Condé, brother of the Lieutenant-General and the suspected architect of the Amboise conspiracy, had already prepared for war and, taking Wassy as the pretext, assumed the role of a protector of Protestantism and began to seize and garrison strategic towns along the Loire Valley.

After the military leaders of both sides were either killed or captured in battles at Rouen, Dreux, and Orléans, the regent mediated a truce and issued the Edict of Amboise (1563).

[16] The war was followed by four years of an uneasy "armed peace", during which time Catherine united the factions in the successful effort to recapture Le Havre from the English.

Their tour spanned two years and brought them through Bar, Lyon, Salon-de-Provence (where they visited Nostradamus), Carcassonne, Toulouse (where the King and his younger brother Henry were confirmed), Bayonne, La Rochelle, and Moulins.

The Battle of Saint-Denis resulted in a Huguenot defeat and the death of Anne de Montmorency, the royal commander-in-chief, and the short war ended in 1568 with the Peace of Longjumeau.

The Dutch Republic, England and Navarre intervened on the Protestant side, while Spain, Tuscany and Pope Pius V supported the Catholics.

[24] After the conclusion of the Peace of Saint-Germain-en-Laye in 1570, the king increasingly came under the influence of Admiral Gaspard de Coligny, who had succeeded the slain Prince of Condé as leader of Huguenots after the Battle of Jarnac in 1569.

On 22 August, a failed attempt on Coligny's life put the city in a state of apprehension, as both visiting Huguenots and Parisian Catholics feared an attack by the other side.

[27] Charles' physical condition, tending towards tuberculosis, deteriorated to the point where, by spring of 1574, his hoarse coughing turned bloody and his hemorrhages grew more violent.