The susceptibility to antimicrobials of bacterial isolates from dogs (n = 1256) and cats (n = 94) was retrospectively evaluated in a veterinary diagnostic laboratory over a 4-year period (2016–2019). Out of 1316 isolates in dogs, 771 were Staphylococcus spp. distributed as follows: Staph. pseudointermedius (n = 406), Staph. intermedius (n = 160), Staph. aureus (n = 104), and Staph. coagulase-negative (n = 101). In common, all Staphylococcus spp. showed a high prevalence (20–50%) of resistance to ampicillin, cephalosporin, enrofloxacin, gentamicin, tetracycline, and trimethoprim-sulfonamide, but a low prevalence (1–10%) of resistance to amoxicillin-clavulanate. With regards to the other families of bacteria, the number of antimicrobials for which resistance was high (>20%) in dogs was: Enterobacteriaceae (7/12), Enterococcus spp. (10/16), E. coli (11/15), Pseudomonas spp. (10/13), and Streptococcus spp. (4/9). For urinary tract infections caused by E. coli or Enterobacteriaceae (Klebsiella spp., Proteus spp.), amikacin and florfenicol were the only drugs that demonstrated 100% in vitro efficacy. Multi-drug resistance was observed in 18.7% (246/1316) and 22% (21/97) of the isolates from dogs and cats, respectively. Except for Pseudomonas spp., known for intrinsic resistance, resistance in other bacteria was likely attributed to high selection pressure. In conclusion, empirical antimicrobial use cannot be recommended to treat most common infections, and selection should be based on results from susceptibility testing.