Ciprofloxacin is a critically important antibiotic for human health. The increase of Escherichia coli resistance to ciprofloxacin is a global public health problem due to its importance in the treatment of complicated urinary tract infections and other serious infections; however, its prescription is high in the Colombian Caribbean. The objective was to determine the resistance trend of E. coli to ciprofloxacin in a Colombian hospital of high complexity. From antibiogram reports, isolates were categorized according to Clinical and Laboratory Standards Institute criteria for each year studied; proportions were calculated and differences in sensitivity were explored using the χ2 test. The Cochran-Armitage test was used to evaluate the resistance trend. Significance was considered when p-value ≤ 0.05. In total, 6,848 isolates were analyzed, and 49.31% resistance was found. According to origin, the highest resistance was in community samples (51.96% - 95%CI: 50.51; 53.41), and by type of sample, in skin and tissues (61.76% - 95%CI: 56.96; 66.35) and urine (48.97% - 95%CI: 47.71; 50.23). Increasing trends were observed for resistance per year (p < 0.0001), community samples (p = 0.0002) and urine (p < 0.0001). Resistance to ciprofloxacin is high and tends to increase in the community and in urine, exceeding the limit established for its use at the ambulatory level, which is of concern due to the high prescription of fluoroquinolones in the locality.