Background <p>Increasing evidence suggests that the gut microbiome may play an important role in the development of colorectal tumors. Antibiotic use can affect the gut microbiome and may increase the risks of benign and malignant colorectal tumors.</p> Methods <p>Eligible studies assessing the relationship between antibiotic exposure and the risk of developing benign or malignant colorectal tumors were identified. Odds ratios (ORs) were pooled for antibiotic use versus no use using a random-effects model. Further subgroup and sensitivity analyses were conducted to confirm the consistence and robustness of the main findings. The study protocol was registered with PROSPERO.</p> Results <p>Twenty-three studies including 1,145,853 participants were finally included in the analysis. People who had used antibiotics had a 13% increased risk of colorectal tumors compared with those who had never used antibiotics [OR: 1.13; 95% confidence interval (CI) 1.04–1.22; P &lt; 0.01]. Subgroup analysis showed that antibiotic exposure was associated with increased risks of both benign (OR: 1.13; 95% CI 1.00–1.27; P &lt; 0.01) and malignant colorectal tumors (OR: 1.13; 95% CI 1.03–1.23; P &lt; 0.01). In addition, colorectal tumor risk was significantly increased by antibiotic exposure, especially the use of combined antibiotics and a longer period after antibiotic exposure. The main findings were consistent and robust across most subgroups and sensitivity analyses.</p> Conclusions <p>The current findings suggested that antibiotic use increased the risk of developing benign or malignant colorectal tumors. These results highlighted the need for clinicians to prescribe antibiotics cautiously, to reduce colorectal cancer risk.</p>