Ian Brown, 44, and Daniel Dunkley, 35, took their own lives at HMP Woodhill last July.
Their relatives claimed Woodhill's governor had not complied fully with Prison Service Instructions (PSIs).
The governor and Justice Secretary Liz Truss said the judicial review claim was "neither appropriate or necessary".
PSIs cover management of prisoners at risk of harm to themselves, to others and from others, early days in custody and medical emergency response codes.
Heather Williams QC, for the families, said the claim addressed what she said was an "exceptionally high" rate of self-inflicted deaths at the Milton Keynes prison.
Seven prisoners killed themselves last year, five in 2015, with 18 in total since May 2013.
Ms Williams said the case raised serious ongoing breaches of Article 2 of the Human Rights Act, which protects the right to life, and involved long-term failures to comply with the responsibility placed on the authorities to protect prisoners.
James Strachan QC, defending, said: "Not only have the governor and the secretary of state taken significant action in 2016 to improve the situation, but this is a continuing high priority."
Lord Justice Irwin and Mr Justice Garnham rejected the judicial review claim.
In their ruling, they said the families had failed to establish a "systemic failing".
Mr Justice Garnham said: "The defendants have made it clear that they share the great concern of the claimants about the rate of suicides in prisons generally, and HMP Woodhill in particular.
"They have in place sensible and satisfactory policies.
"The defendants have acknowledged that, on occasions, operational errors have been made by their staff in dealing with those at risk of suicide and have sought to prevent those mistakes being repeated."

Iran international Ghoochannejhad, 28, scored five goals in 42 appearances after joining the Addicks in 2014.
Former Juventus defender Motta, 30, featured 12 times following his move to The Valley in February.
Marko Dmitrovic, Alou Diarra and Callum Harriott have triggered one-year extensions to their current deals.
Meanwhile, the south-east London club have offered a new contract to 20-year-old goalkeeper Dillon Phillips.
Development squad players Zak Ansah, Alex Kelly, Ayo Obileye, Josh Staunton and Joe Pigott will also leave Charlton, who finished 22nd in the Championship this season and dropped back into League One following four years in the second tier.
Jose Riga left his position of head coach following the final game of the season and the Addicks are yet to appoint a new boss.
Northampton's Chris Wilder was approached to succeed the Belgian but turned the job down and joined Sheffield United instead.
Families of two men who died in prison have lost a High Court case related to the high rate of suicides there.
[NEXT_CONCEPT]
Forward Reza Ghoochannejhad and full-back Marco Motta will leave relegated Charlton Athletic when their contracts expire this summer.