Half-centuries from Tom Kohler-Cadmore and Brett D'Oliveira helped Worcestershire post a competitive total, but Rikki Clarke led the reply, scoring the winning runs to finish on an unbeaten 52 with just three balls remaining.
A 112-run opening partnership from Daniel Bell-Drummond and Joseph Denly led the hosts to a total of 173, but Jamie Overton and Abdur Rehman were the only players to score more than 30 for Somerset as the visitors failed to get close to their opponents' score.
The visitors would have been confident of victory after Graham Clark scored an unbeaten 91 to lead Durham to a score of 191.
Yorkshire made a shaky start to their reply, with Aaron Finch out for a duck off the first delivery before the team slipped to 28-3, but Bairstow led the recovery, hitting 92 off 42 balls, before Tim Bresnan hit the winning runs.
Sussex Sharks have kept the pressure on the South Group leaders with an emphatic win over Glamorgan.
Horton finished as the top scorer with 63 as the visiting side posted a score of 191, before Jordan Clark claimed three wickets to ensure that Leicestershire fell well short in their reply.
Hamish Rutherford and Wayne Madsen ensured that the visitors came close, needing three for victory off the final ball, but Madsen could not add further to his unbeaten 51 to edge Derbyshire across the line.
The visitors were bowled out for just 109 as Steven Finn ripped through the top order, finishing with figures of 4-28, allowing Nicholas Gubbins and Eoin Morgan to lead Middlesex past the total with three overs to spare.
Results in full:
Lancashire Lightning (195-5) beat Leicestershire Foxes (151-8) by 40 runs
Middlesex Panthers (110-4) beat Essex Eagles (109 all out) by six wickets
Birmingham Bears (161-5) beat Worcestershire Rapids (160-5) by five wickets
Nottinghamshire Outlaws (176-6) beat Derbyshire Falcons (170-4) by two runs
Yorkshire Vikings (194-5) beat Durham Jets (191-6) by five wickets
Kent Spitfires (173-6) beat Somerset (151-9) by 22 runs
Hampshire (186-5) beat Surrey (157-9) by 29 runs