Seanad Éireann (2002–2016)

Following his election to the Seanad in 2002, he was appointed Seanad Spokesperson on Communications, Marine and Natural Resources.^[13] He was re-elected in 2007 and was appointed Seanad Spokesperson on Finance.^[14]

On 31 January 2011, prior to that year's general election, MacSharry was appointed to the Fianna Fáil frontbench by the new party leader Micheál Martin, as Spokesperson on Tourism and Arts. MacSharry was a candidate at the 2011 general election in the Sligo–North Leitrim constituency, but was not elected.^[14] He was re-elected to the Seanad in April 2011 and was appointed Fianna Fáil Seanad Spokesperson on Health.

Following the financial crisis of 2007–2008 and the consequent mortgage arrears crisis which ensued in Ireland, MacSharry co-founded the prevention of family home repossessions group, advocating for the protection of the family home.^[15]

MacSharry introduced the Family Home Bill 2011 in July 2011 in the Seanad, which would effectively have prevented the granting of an order for the repossession of a primary family residence except in very exceptional circumstances where borrowers were in difficulty due exclusively to willful neglect. The bill was narrowly defeated in the Seanad.^[16]

In 2012, collaborating with Seanad colleague and professor of oncology at St Vincent's Hospital in Dublin, John Crown, MacSharry introduced the Access to Cancer Treatment Bill to the Seanad which sought to simplify the approval process to ensure early access for patients to avail of expensive breakthrough cancer drugs.^[17][18] The bill was defeated by one vote.^[17][18]

MacSharry authored a Fianna Fáil policy paper in February 2013 entitled, Actions Speak Louder than Words, which promoted the case for and approach to be taken for a reduction in loss of life through suicide by 30 percent.^[19] To progress proposals to increase funding for suicide prevention and mental health measures, he introduced the Suicide Prevention and Mental Health Fund Bill in 2014 to the Seanad which was defeated.^[20]

Dáil Éireann (2016–present)

In the 2016 general election, MacSharry was elected on his second attempt, topping the poll in the newly reformed Sligo–Leitrim constituency with 8,856 votes (14.2%), to take a seat in the constituency his father Ray had served in.

In 2018, the Dáil was suspended for ten minutes because of an allegedly anti-semitic remark made by MacSharry. While discussing the reduction of hours in a Garda station in Donegal town, MacSharry alleged that the government was like Nazi propaganda minister Joseph Goebbels, and shouted "Goebbels" at the government's benches. Minister for Justice Charles Flanagan and Minister for Health Simon Harris called on MacSharry to withdraw the remark, with Harris calling the comment "anti-semitic" and "an attack on the Jewish Community", but MacSharry's Fianna Fáil colleague, Ceann Comhairle Sean O Fearghail, did not call on MacSharry to withdraw the remark.^[21]

In 2020, MacSharry was re-elected in the same constituency, albeit with a reduced share of 7,004 votes (11.5%), being elected on the final count over his Fianna Fáil running mate Eamon Scanlon.

MacSharry caused controversy in 2020 when he accused public servants of "laziness" and said they were "using the COVID-19 crisis as an excuse to "lie on the couch and watch box sets". The Association of Higher Civil and Public Servants called on MacSharry to withdraw the remark, calling it "ill-informed and ill-considered" and requesting an apology from MacSharry, but MacSharry refused to, saying "Of course, such comments aren't popular, but it needs to be said."^[22][23]

MacSharry criticised Fáilte Ireland and his Fianna Fáil colleague at the time Stephen Donnelly on the public health guidelines they had issued regarding the opening of pubs and restaurants across Ireland, comparing them to the East German intelligence agency the Stasi.^[24][25]

In January 2021, MacSharry attracted further controversy for his comments made during a Fianna Fáil parliamentary party meeting, in which he said that "if the Ku Klux Klan were selling a COVID-19 vaccine, Ireland should buy it".^[26][27]

During his time in Fianna Fáil, MacSharry was very critical of Micheál Martin, calling on him to resign as leader of Fianna Fáil multiple times. He first called on Martin to resign in June 2021 after it had emerged Fianna Fáil had used covertly polled voters while pretending to be independent pollsters.^[28] In July 2021, MacSharry again called on Martin to resign after Fianna Fáil's poor performance in the 2021 Dublin Bay South by-election, in which Fianna Fáil's candidate Deidre Conroy received under 5 percent of the vote.^[29] It was revealed that month that MacSharry was seeking out TDs in his party to put forward a motion of no confidence in Martin.^[30]

MacSharry published a paper, Now More Than Ever in July 2021 on the impact of COVID-19 related restrictions on the mental health of society suggesting no further lockdowns should be considered.^[31]

On 15 September 2021, MacSharry resigned from the Fianna Fáil parliamentary party in order to vote against Simon Coveney of Fine Gael in a motion of no confidence resulting from the Katherine Zappone controversy.^[4]

On 2 November 2022, MacSharry was prevented from rejoining Fianna Fáil following a row over the handling of a bullying complaint against him.^[5]

On 18 October 2023, MacSharry announced that he would not contest the next general election.^[32]