Background: A correct approach to recurrent urinary tract infections (rUTIs) is an important pillar of antimicrobial stewardship. We aim to define an Artificial Neural Network (ANN) for predicting the clinical efficacy of the empiric antimicrobial treatment in women with rUTIs. Methods: We extracted clinical and microbiological data from 1043 women. We trained an ANN on 725 patients and validated it on 318. Results: The ANN showed a sensitivity of 87.8% and specificity of 97.3% in predicting the clinical efficacy of empirical therapy. The previous use of fluoroquinolones (HR = 4.23; p = 0.008) and cephalosporins (HR = 2.81; p = 0.003) as well as the presence of Escherichia coli with resistance against cotrimoxazole (HR = 3.54; p = 0.001) have been identified as the most important variables affecting the ANN output decision predicting the fluoroquinolones-based therapy failure. A previous isolation of Escherichia coli with resistance against fosfomycin (HR = 2.67; p = 0.001) and amoxicillin-clavulanic acid (HR = 1.94; p = 0.001) seems to be the most influential variable affecting the output decision predicting the cephalosporins- and cotrimoxazole-based therapy failure. The previously mentioned Escherichia coli with resistance against cotrimoxazole (HR = 2.35; p < 0.001) and amoxicillin-clavulanic acid (HR = 3.41; p = 0.007) seems to be the most influential variable affecting the output decision predicting the fosfomycin-based therapy failure. Conclusions: ANNs seem to be an interesting tool to guide the antimicrobial choice in the management of rUTIs at the point of care.