Guardians vs. Cardinals Prediction, Odds, Probable Pitchers, Prop Bets for Wednesday, April 15

The rubber match of a three-game set between the Cleveland Guardians and St. Louis Cardinals takes place on Wednesday afternoon, and the Cardinals are slight favorites at home.

Cleveland picked up a 9-3 win in the series opener on Monday, but the Cards moved back over .500 with a 6-5 win on Tuesday night. Both teams have negative run differentials early in the 2026 season, though the Guardians are just a game out of first in the AL Central.

On Wednesday, right Slade Cecconi (5.74 ERA) gets the ball for the Guardians for the fourth time this season, and he’s looking to bounce back after a poor outing in a loss to Atlanta on April 10.

Meanwhile, Dustin May (9.45 ERA) is on the mound for the Cardinals, and his MLB career could be hanging in the balance this season after injuries and poor performance have landed him on his third team since the start of 2025.

Let’s take a look at the odds, a player prop to bet and my prediction for this interleague clash on Wednesday afternoon.

Guardians vs. Cardinals Odds, Run Line and Total

Odds via DraftKings Sportsbook

Run Line

Guardians -1.5 (+146)
Cardinals +1.5 (-177)

Moneyline

Guardians: -108
Cardinals: -112

Total

8.5 (Over -115/Under -105)

Guardians vs. Cardinals Probable Pitchers

Cleveland: Slade Cecconi (0-2, 5.74 ERA)
St. Louis: Dustin May (1-2, 9.45 ERA)

Guardians vs. Cardinals How to Watch

Date: Wednesday, April 15
Time: 1:15 p.m. EST
Venue: Busch Stadium
How to Watch (TV): Cardinals.TV/Guardians.TV
Guardians record: 10-8
Cardinals record: 9-8

Guardians vs. Cardinals Best MLB Prop Bet

Cardinals Best MLB Prop Bet

Jordan Walker to Hit a Home Run (+301)

Earlier today, I shared in SI Betting’s best home run props column – Daily Dinger – why Walker is worth a look to stay hot:

St. Louis Cardinals youngster Jordan Walker is off to an insane start this season, hitting .328 with eight home runs, including five homers against right-handed pitching.

Walker has homered four times in his last six games, posting a 375 batting average and a 1.298 OPS during that stretch. So, I think he’s worth a bet to stay hot on Wednesday against the Cleveland Guardians.

Cleveland has righty Slade Cecconi on the mound, and he’s off to a slow start in 2026. Cecconi has a 5.74 ERA and has given up three homers in three starts. In his career, Cecconi has struggled to limit the long ball, giving up 47 homers in 53 games (43 starts), including 24 homers in 23 appearances in 2025.

Walker has simply been too hot to pass up at this number on Wednesday.

Guardians vs. Cardinals Prediction and Pick

Both of these starting pitchers have struggled in the 2026 season, as Cecconi has allowed at least five runs in two of his outings while May is allowing over one run per inning pitched.

Cecconi does have six innings of one-hit ball in a loss to the Chicago Cubs sandwiched in between two rough outings, but I don’t see him completely turning things around against a Cardinals team that is 14th in MLB in runs scored.

The Guardians and Cardinals are both in the middle of the pack in runs scored and OPS, so this isn’t exactly a game for either starter to get back on track.

May has given up six, seven and two runs in his three starts, failing to complete five innings in two of them. The bullpens have also struggled for both squads, as the Cards have a 5.27 bullpen ERA while the Guardians are slightly better at 4.83.

On top of that, the OVER has gone 10-6-1 in St. Louis’ games in 2026.

I’m expecting a high-scoring affair in this series finale after these teams combined for 12 and 11 runs on Monday and Tuesday.

Pick: OVER 8.5 (-115 at DraftKings)

Odds refresh periodically and are subject to change.

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