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."
Families of two men who died in prison have lost a High Court case related to the high rate of suicides there.