The two teams met in the second round of the same tournament last season, with Wednesday's visitors eventually prevailing on their way to winning the trophy.
Match preview
Port Vale headed into the new season on the back of a promotion to League One, as they prevailed in last season's playoffs in England's fourth tier, beating Swindon Town on a penalty shootout in the semi-final before triumphing with a 3-0 win over Mansfield Town at Wembley in May.
The Staffordshire outfit were not so successful in their penalty shootout when they met Rotherham United in last year's EFL Cup, though, as David Amoo's miss from the spot proved costly after he had equalised in the dying embers of regular time to see the contest end 1-1.
Life back in the third tier began well for Darrell Clarke's men, as Nathan Smith and Connor Hall hit first-half goals in an opening-day 2-1 win at home to Fleetwood Town, but they were unable to make it two from two away at Exeter City on Saturday.
Harry Kite and Jevani Brown put their hosts 2-0 up in the first half, and Brown would hit his second before Sam Nombe added a fourth in the final 15 minutes to send Port Vale home empty-handed following a 4-0 thrashing.
Now hoping to bounce back from that heavy defeat, Clarke's men will hope to avenge last year's defeat and progress with what would be an eye-catching triumph over Championship opposition.
Rotherham United will make the trip hoping to take the first step towards retaining the title they won at Wembley last season.
In the midst of their promotion-winning campaign in League One, Paul Warne's side progressed through to the semi-finals with wins over Port Vale, Crewe Alexandra and Cambridge United - the latter and former of which being after penalty shootouts.
After seeing off Hartlepool United in another shootout, the Millers met Sutton United in the final in April, and they would go behind twice, with Ben Wiles firstly levelling the game at a goal apiece before Jordan Osei-Tutu forced a period of extra time with a 96th-minute equaliser.
Chiedozie Ogbene would give his side the lead for the first time in the game early in the added 30 minutes, before Michael Ihiekwe sealed their victory with a fourth goal eight minutes from time to see Warne's men return to South Yorkshire with their first piece of silverware since 1996.
Upon their return to the Championship this season, the Millers began with a creditable point at home to Swansea City last week, with Ogbene opening the scoring in a 1-1 draw, before their scheduled away game against Coventry City was postponed last weekend, and they will now look to progress in the EFL Cup with a win on their travels on Wednesday before turning their attention back to England's second tier with a home game against Reading looming.
Port Vale form (all competitions):
Rotherham United form (all competitions):
Team News
Port Vale will likely remain without last season's top scorer James Wilson, who has missed their first two games of the season with a knock.
In his absence, Jamie Proctor should again spearhead the attack, likely alongside Tom McDermott.
Elsewhere, Ben Garrity and Harry Charsley continue to be key men in the engine room, while Lewis Cass, Nathan Smith and Connor Hall should line up as a back three.
Paul Warne may use the cup game as an opportunity to take a look at some of his players who did not start in their league opener against Swansea City, with the likes of Peter Kioso, Cohen Bramall and Georgie Kelly set to feature from the outset at Vale Park.
Grant Hall made his debut for the club in that game following a loan move from Middlesbrough and should again start on Wednesday, while Jamie McCart may be brought in if Richard Wood is preserved for the Championship game against Reading.
New striker Tom Eaves will not feature due to an ongoing injury, leaving Conor Washington to lead the line alongside Kelly, while Ben Wiles and Chiedozie Ogbene may also sit out with the weekend in mind.
Port Vale possible starting lineup:
Stone; Cass, Smith, Hall; Worrall, Charsley, Garrity, Ojo, Benning; McDermott, Proctor
Rotherham United possible starting lineup:
Johansen; McCart, Hall, Humphreys; Kioso, Barlaser, High, Lindsay, Bramall; Washington, Kelly