<b><i>Objectives:</i></b> The present study aimed to identify significant causes of readmission within 30 days following coronary artery bypass graft (CABG) surgery and compare readmission incidence related to surgical site infections (SSIs) before and after implementing international recommendations for antibiotic prophylaxis. <b><i>Methods:</i></b> We analyzed 2,225 CABG patients who received either guideline-directed antibiotic prophylaxis (GDAP = 568) or institutional antibiotic prophylaxis (non-GDAP = 1,657) between January 2017 and December 2019. The primary outcome was a composite of sternal wound infection (SWI) or harvest SWI. Secondary outcomes consisted of the individual components of composite end point, the incidence of in-hospital SSIs, and prolonged postoperative length of hospital stay (LOS) (&#x3e;7 days). Propensity matching was used to select pairs for final comparison. <b><i>Results:</i></b> Before implementing GDAP, the most frequent reason for readmission were SSIs, causing 58.2% of all readmissions within 30 days. Of 429 matched pairs, 48 patients in the GDAP group and 67 patients in the non-GDAP group were readmitted to a hospital within 30 days for any cause (11.2 vs. 15.6%, <i>p</i> = 0.048). We found a decreased readmission incidence for reasons related to SSIs, although these differences did not reach statistical significance (7.4 vs. 10.0%, <i>p</i> = 0.069). Adherence to GDAP was associated with reduced in-hospital risks of SSIs and prolonged postoperative LOS (19.6 vs. 26.6%, <i>p</i> = 0.015). <b><i>Conclusions:</i></b> In this contemporary clinical practice study, the adherence to GDAP was an insufficient measure to decrease rehospitalization due to SSIs. The present findings warrant further investigation on factors that may contribute to SSIs development after hospital discharge.