Context: Cotrimoxazole is one of the antibiotics commonly used to treat urinary tract infections. The widespread use of this drug has led to increased resistance to cotrimoxazole among urinary tract pathogens. This study aimed to investigate the cotrimoxazole resistance pattern of uropathogenic bacteria by a systematic review and meta-analysis method. Evidence Acquisition: Several databases including PubMed, Web of Science, Scopus, Google Scholar, Iran Medex, Magiran, IranDoc, MedLib, and SID were searched. From a total of 171 papers published from different regions of Iran from 1992 to May 2015, 67 were included in this study. To assess the quality of the study, the STROBE (strengthening the reporting of observational studies in epidemiology) checklist was employed. The I2 index was used to determine heterogeneity and a random effects model to analyze the data. Results: The results showed that the prevalence of urinary tract infection was several times higher in women than in men. The most common pathogens causing urinary tract infections were E. coli 64%, Klebsiella 12%, Staphylococcus 10%, and Enterobacter (6%). The prevalence of cotrimoxazole resistance was as follows: E. coli 62% (95%CI: 60-65), Klebsiella 54% (95% CI: 45-62), Staphylococcus 55% (95% CI: 47-63), and Enterobacter 52% (95% CI: 33-70). Cotrimoxazole resistance in different studies varied from 22% in Arak to 88% in Ahvaz. Conclusions: Gram-negative bacilli, particularly Escherichia coli, were the most common bacteria causing urinary tract infections. The majority of strains were resistant to cotrimoxazole. According to the findings, cotrimoxazole is not recommended as the firstline drug for the treatment of urinary tract infections in Iran.