John Milburn, 19, of Crosby, and 47-year-old Andrew Glaister from the Isle of Man, became ill after taking the drug during the Cream event on 26 December at the Nation club.
Liverpool Coroner Simon Holder ruled both men had died due to MDMA toxicity.
He said their deaths were "a bizarre coincidence", the Liverpool Echo reported, as the men were unacquainted.
They may have obtained the drug from different people, the inquest heard.
Mr Glaister, who ran his own haulage company, had been drinking in Liverpool bars before the event.
During this time, he purchased two green ecstasy tablets, his brother Chris Glaister told the hearing.
Det Insp Lee Wilkinson, of Merseyside Police, said officers had been unable to establish who sold ecstasy to Mr Milburn.
However, in a statement read by the coroner, his friend Jamie Maclean said they had bought orange-coloured tablets from "a local lad".
Mr Milburn died in hospital the day after being taken ill at the club night, while Mr Glaister died on 29 December.
No-one has been charged in connection with the deaths, Det Insp Wilkinson said.
Regarding Mr Milburn's death, the coroner said: "The medical evidence is sadly very clear. The reason John is not with us is because he took MDMA.
"John is an adult and he took that decision, but his body couldn't withstand it that particular night."
Mr Glaister's death was a "tragic coincidence", he said.
Mr Holder said he was satisfied the club "did everything it could" to help the men, who were seen by trained door staff and medics.
Cream, known as a "super club", first opened its doors at the Nation venue in Wolstenholme Square in 1992, before branching out into Cream Ibiza and the Creamfields festival.
The Boxing Day event was held prior to the closure of Nation, which is to be replaced by a new music venue.
Two men who died after becoming ill at a club night in Liverpool had taken ecstasy, an inquest has concluded.