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First Italian War of Independence

Garibaldi returned to Italy amidst the turmoil of the revolutions of 1848 in the Italian states and was one of the founders and leaders of the Action Party. Garibaldi offered his services to Charles Albert of Sardinia, who displayed some liberal inclinations, but he treated Garibaldi with coolness and distrust. Rebuffed by the Piedmontese, he and his followers crossed into Lombardy where they offered assistance to the provisional government of Milan, which had rebelled against the Austrian occupation. In the course of the following unsuccessful First Italian War of Independence, Garibaldi led his legion to two minor victories at Luino and Morazzone.

After the crushing Piedmontese defeat at the Battle of Novara on 23 March 1849, Garibaldi moved to Rome to support the Roman Republic recently proclaimed in the Papal States. However, a French force sent by Louis Napoleon threatened to topple it. At Mazzini's urging, Garibaldi took command of the defence of Rome. In fighting near Velletri, Achille Cantoni saved his life. After Cantoni's death, during the Battle of Mentana, Garibaldi wrote the novel Cantoni the Volunteer.

On 30 April 1849, the Republican army, under Garibaldi's command, defeated a numerically far superior French army at the Porta San Pancrazio gate of Rome. Subsequently, French reinforcements arrived, and the Siege of Rome began on 1 June. Despite the resistance of the Republican army, the French prevailed on 29 June. On 30 June the Roman Assembly met and debated three options: surrender, continue fighting in the streets, or retreat from Rome to continue resistance from the Apennine mountains. Garibaldi, having entered the chamber covered in blood, made a speech favouring the third option, ending with: Ovunque noi saremo, sarà Roma ("Wherever we will go, that will be Rome").

The sides negotiated a truce on 1–2 July, Garibaldi withdrew from Rome with 4,000 troops, and ceded his ambition to rouse popular rebellion against the Austrians in central Italy. The French Army entered Rome on 3 July and reestablished the Holy See 's temporal power. Garibaldi and his forces, hunted by Austrian, French, Spanish, and Neapolitan troops, fled to the north, intending to reach Venice, where the Venetians were still resisting the Austrian siege. After an epic march, Garibaldi took temporary refuge in San Marino, with only 250 men having not abandoned him. Anita, who was carrying their fifth child, died near Comacchio during the retreat.