OBJECTIVE: Urinary tract infections (UTIs) are common in primary care. The yield of urine cultures in patients with UTI symptoms can be considerably different between high-income and low-income settings. This study aimed to explore possible causes of negative urine cultures in patients presenting with symptoms of UTI to primary health clinics in Harare. DESIGN: Cross-sectional study. SETTING: Nine primary health clinics in Harare, Zimbabwe. PARTICIPANTS: Adults presenting with symptoms of UTIs between March and July 2020. PRIMARY OUTCOME MEASURES: Urine samples underwent dipstick testing, microscopy, culture, and testing for sexually transmitted infections (STIs) using GeneXpert and for the presence of antibiotic residues using an antibiotic bioassay. The primary outcomes were the number and proportion of participants with evidence of STIs, prior antibiotic exposure, leucocyturia and UTIs. RESULTS: The study included 425 participants with a median age of 37.3 years, of whom 275 (64.7%) were women. Leucocyturia was detected in 130 (30.6%, 95% CI 26.2% to 35.2%) participants, and 96 (22.6%, 95% CI 18.7% to 26.9%) had a positive urine culture for a uropathogen. Chlamydia trachomatis, Neisseria gonorrhoeae and Trichomonas vaginalis were detected in 43/425 (10.1%, 95% CI 7.4% to 13.4%), 37/425 (8.7%, 95% CI 6.2% to 11.8%) and 14/175 (8.0%, 95% CI 4.4% to 13.1%) participants, respectively. Overall, 89 (20.9%, 95% CI 17.2% to 25.1%) participants reported either having taken prior antibiotics or having had a positive urine bioassay. In 170 (40.0%, 95% CI 35.3% to 44.8%) participants, all of the tests that were performed were negative. CONCLUSIONS: This study found a high prevalence of STIs and evidence of prior antimicrobial use as possible explanations for the low proportion of positive urine cultures.