Purpose: Urinary tract infections (UTIs) are widespread and affect a large portion of the human population. Cranberry juices and extracts have been used for UTI prevention due to their content of bioactive proanthocyanidins (PACs), particularly of the A type (PAC-A). Controversial clinical results obtained with cranberry are often due to a lack of precise determination and authentication of the PAC-A content. This study used OximacroReg. (Biosfered S.r.l., Turin, Italy), a cranberry extract with a high content of PAC-A, to prevent UTIs in female and male volunteers. Materials and Methods: The OximacroReg. PACs content was assayed using the Brunswick Laboratories 4-dimethylaminocinnamaldehyde (BL-DMAC) method, and the dimer and trimer PACs-A and PACs-B percentages were determined via high-performance liquid chromatography/electrospray ionization tandem mass spectrometry (HPLC/ESI-MS/MS). A balanced group of female (ranging from 19 to over 51 years) and male volunteers (over 51 years) was divided into two groups. The experimental group received 1 capsule containing OximacroReg. (36 mg PACs-A) twice per day (morning and evening) for 7 days, and the placebo group was given the same number of capsules with no PACs. Results: Analysis of OximacroReg. revealed a high total PAC content (372.34 mg/g+or-2.3) and a high percentage of PAC-A dimers and trimers (86.72%+or-1.65). After 7 days of OximacroReg. administration, a significant difference was found between the placebo and OximacroReg. groups for both females (Mann-Whitney U-test=875; P=.001; n=60) and males (Mann-Whitney U-test=24; P=.016; n=10). When the female and male age ranges were analysed separately, the female age range 31-35 showed only slightly significant differences between the placebo and OximacroReg. groups (Mann-Whitney U-test=20.5; P=.095; n=10), whereas all other female age ranges showed highly significant differences between the placebo and OximacroReg. groups (Mann-Whitney U-test=25; P=.008; n=10). Furthermore, colony forming unit/mL counts from the urine cultures showed a significant difference (P<.001) between the experimental and the placebo groups (SD difference=51688; df=34, t=-10.27; Dunn-Sidak Adjusted P<.001, Bonferroni Adjusted P<.001). Conclusion: Careful determination of the total PAC content using the BL-DMAC method and the authentication of PACs-A with mass spectrometry in cranberry extracts are necessary to prepare effective doses for UTI prevention. A dose of 112 mg OximacroReg. containing 36 mg PACs-A was found to be effective in preventing UTIs when used twice per day for 7 days.