He decided not to seek a second term there, and instead ran for mayor of Lisbon in the 2001 local elections, defeating the incumbent João Soares and becoming one of the biggest surprises of the electoral night.

"[2] The situation inherited by Santana Lopes was a little better, as the previous government led by Barroso had been able to comply with European Union directives regarding the deficit by selling state assets.

Santana Lopes' period in office was also marked by chaos in the allocation of teachers to schools[citation needed] (more than a month after classes officially started, and resulting from alleged incompetence of the IT provider (designated during the previous Government); the problem was swiftly solved by another small provider), and by claims of pressure exerted on the press, including arranging for the replacement of the information director of the public television channel RTP, and pressing private television channel TVI to tone down the criticism of him by a political commentator, Marcelo Rebelo de Sousa,[citation needed] a former leader of his own party, who consequently left the channel.

Santana Lopes' demise as head of government was sealed on 30 November 2004 when President Jorge Sampaio, a member of the opposing party, announced that he was calling an early Parliament election for February 2005, from which a new government would be formed, after Henrique Chaves, a Santana loyalist, resigned after four days as Minister for Sport, claiming that he lacked "loyalty and truth".

[3] In September 2011, Santana Lopes was nominated by Prime Minister Pedro Passos Coelho to assume leadership of Santa Casa da Misericórdia de Lisboa, a charity that runs Portugal's national lottery.

[4] He resigned leadership of Santa Casa da Misericórdia de Lisboa in order to do so, but was defeated by Rui Rio.

They were heading to a campaign rally in Cascais after an event in Coimbra when, between Soure and Pombal, Santana fell asleep and lost control of the vehicle, a Lexus GS rented in name of his law firm.

The car slid slowly to the left, hitting the central reservation barrier and veering abruptly to the right, crashing out of the road and tumbling several times before coming to a standstill in an overturned position.

Santana Lopes would only be removed from the wreckage by the emergency services, and was transported by helicopter to Coimbra hospital, to where Sande was also taken on an ambulance.

[19] This line of thought proved to be flawed as the party performed considerably worse, obtaining only 0,77% of the vote on national level and electing no MPs.

[20] Without further national elections in the near future, and with all the objectives unachieved, Santana Lopes suspended his executive functions as Alliance's leader on 15 May 2020, and announced a period of reorganisation of the party.

[24] After Santana's announcement that he was leaving Alliance leadership, rumours started circulating that he could be preparing a return to the Social Democratic Party.

[26] His return to the Social Democratic Party was ruled out when it became known, in late March 2021, that he was seeking to create a citizen's group in order to run for mayor of Figueira da Foz, a position he held between 1998 and 2001.

The candidate of the Social Democratic Party, Pedro Machado, launched on 10 August a legal action to invalidate Santana's candidacy due to alleged irregularities in its submission,[29][30] which was rejected by the local court three days later.

Under Portuguese law, the top candidate of the most voted list automatically becomes the mayor, but Santana will have to negotiate with other political groups in order to implement his agenda, since he didn't won a majority.

On his inauguration speech, he announced to have reached a deal with the University of Coimbra to build a campus on Figueira da Foz, dedicated to marine economy and sciences.

[36] On 20 April 2023, and without explicitly assuming a candidacy, Santana Lopes entertained the possibility of being a candidate for President of Portugal on the next election, saying that he saw no one better qualified than himself.

[37] However, he placed himself definitely out of the race on 19 October 2023, few days after the outbreak of the Israel–Hamas war, citing the current state of world affairs as the main reason.