Background Minimally invasive procedures are demanding in terms of cardioprotection. In many leading centres Bretschneider HTK solution is used for mitral valve surgery. The study was designed to provide comparison of the del Nido and Bretschneider HTK protocol. Methods Patients who underwent minimally invasive mitral valve repair for primary mitral regurgitation and received single delivery of either del Nido (Group 1) or Bretschneider HTK cardioplegia (Group 2) were matched on basis of age, gender and length of the cross-clamp time. The groups were compared in terms of major adverse cardiac and cerebrovascular events (death, myocardial infarction, stroke), high sensitivity troponin T (hs-TnT) and creatine kinase- MB isoenzyme (CK-MB) release at 12 h and 24 h following the surgery, incidence of low cardiac output syndrome (LCOS), postoperative arrhythmia, transfusions and postoperative renal function. Results Case control matching selected 38 pairs of patients. None of patients died, nor suffered from myocardial infarction or stroke. Troponin values did not differ at 12 h (median: 281.0 pg/mL vs 313.0 pg/mL; p = .38) and 24 h (median: 261.0 pg/mL vs 299.0 pg/mL; p = .54), as well as CK-MB at 12 h (median: 25.0 ng/mL vs 29.0 ng/mL; p = .31) and 24 h (median: 11.0 ng/mL versus 9.6 ng/mL; p = .46). Difference in occurrence of LCOS was insignificant (2 vs 7; 5.2% vs 18.4%; p =.15). No difference was shown in incidence of postoperative arrhythmia, transfusions and renal function. Conclusions Del Nido cardioplegia can be used safely as an alternative for Bretschneider HTK for minimally invasive mitral valve surgery.