More than 16,000 people have demonstrated in Thessaloniki against the government's economic policies and in opposition to a controversial planned name contract with neighboring Macedonia.
Riot police fired tear gas at around 100 protesters who threw flares and stones.
A preliminary agreement, which will be confirmed by a Skopje referendum later this month and a Greek parliamentary vote in early 2019, will allow the Balkan state to rename the Republic of Northern Macedonia.
The small landlocked country joined the United Nations in 1993 as the former Yugoslav Republic of Macedonia.
Greece also has a northern province called Macedonia, the heart of the ancient kingdom of Alexander the Great, and many Greeks fear that the agreement will officially allow Skopje to reclaim its cultural heritage.
Tsipras insisted on Saturday that Thessaloniki should act as a "cultural bridge, not a fence".
"Thessaloniki does not deserve misery, intolerance, fear, hatred and discord," he said as he promised to donate state land for a new stadium for PAOK, the city's most popular sports club.
The protesters, many of whom waved Greek flags, shouted "Greece, Greece, Macedonia" and "traitors".
They also hurled insults at Tsipras and demanded that he resign.
The opposition parties and the unions dispute that the end of the third rescue of Greece last month leaves many reasons for the celebration.
"(The Greeks) believe that austerity is not over, everything that has ended is the obligation of the creditors to give money to the country (…) and there continues to be a tough guardianship," said Yiannis Panagopoulos, leader of the leading union. of Greece, GSEE.
Unemployment has fallen below 20 percent for the first time since 2011, but most Greeks continue to struggle under heavy taxes and a drastic reduction in income.