The most prosperous time in Pisa's history – well testified by wonderful buildings of the square Piazza dei Miracoli, such as the cathedral, the tower and the baptistery – is surely the 12th century; after the success of the first crusade to the Holy Land between 1096 and 1099, the town opens its own trade agencies in middle east, starting to import precious materials and improving its traffics.

Pisa's fleet is amongst Italy's most efficient ones; between 1113 and 1124 Pisa defeats the Saracens at the battle by the Balearic islands, and again (between 1134 and 1137) after the victory in the war against Amalfi, it is called by the Emperor Barbarossa to control the whole Tyrrhenian coast from Porto Venere to Civitavecchia.
From the second half of the 12th century and again, during the 13th century, the Italian, as well as the European political situation is slowly deteriorating: the Italian towns suffer from inner divisions, and different disagreements between Pisa and other towns (Lucca, Genoa and Florence) emerge.
Different victories are to be recorded in these years: in 1241 and 1258 against Genoa, allied with Venice in S.Giovanni d'Acri, by Montaperti as an ally of Siena against Florence in 1260. In 1284 the Pisan fleet is nevertheless defeated by Genoa.
Four years later Pisa is forced to give its possessions in Corsica and Sardinia, leaving the middle east colonies and paying a hard tax to Genoa; this causes a popular riot in the city, which will be then repressed by Genoa's and Lucca's armies in 1290.
During the following years Pisa loses its political importance in Italy, mainly because of some leading patrician families in town (Faggiuola, Della Gherardesca and Gambacorta), who were close allies of Florence, and secondly because of different following dominions (Visconti between 1399 and 1406, the French Lords between 1494 and 1509).
Pisa offers a good harbour to Florence, and this brings the Florentine Medici family (especially Lorenzo) to carry out many building works in the city and its territory. Pisa's real decay begins anyway with a simpler, more natural phenomenon: the low disappearance of its harbour, due to the debris come form the river Arno.
The berths slowly become impassable and the brackish lands are soon attacked by malaria; Pisa's population goes back to 8000, and this situation will last until a new land reclamation is done by the grand Duke of Lorena, thanks to new channels between Pisa and Livorno and the enlargement of some buildings which today house the university. This new situation will give a long time of economical and social development to the city of Pisa.