The aim of this prospective study was to identify possible pathogenic organisms associated with wound complications in the form of wound infections, wound breakdown and the formation of oro-nasal fistulas. The organisms’ resistance profile to antibiotics was also evaluated. This prospective study consisted of the evaluation of the intra-oral microbiological profile of 100 babies with soft palate cleft deformities peri-operatively. A wide spectrum of pathogenic organisms from the upper aero-digestive track was isolated, as well as a group of organisms that originated from the colon/perineum. The latter organisms were mostly associated with postoperative complications. The antibiotic resistance profile showed a high resistance to commonly used antibiotics such as ampicillin, amoxycillin-clavulanic acid, and first- and second-generation cephalosporins. The resistance profile of the organisms needs to be reassessed and appropriate antibiotics must be used in combination with an antimicrobial mouth rinse.