Abstract Background Catheter-related thrombosis (CRT) incidence, rate, and risk factors vary in literature due to differences in populations, catheters, diagnostic methods, and statistical approaches. The aim of this single-center, prospective, observational study was to assess incidence, incidence rate (IR), cumulative incidence, and risk factors by means of IR ratio (IRR) of asymptomatic CRT in a non-oncologic Intensive Care Unit (ICU) population. CRT development was assessed daily by means of ultrasound screening. The proportions of patients and catheters developing CRT and CRT incidence rates, expressed as the number of events per catheter-days (cd), were calculated. Kalbfleisch and Prentice’s method was used to estimate the cumulative incidence of CRTs. Univariate and multivariable Poisson regression models were fitted to calculate IRR in risk factors analysis. Results Fifty (25%, 95% CI 19–31) out of 203 included patients, and 52 (14%, 95% CI 11–18) out of 375 catheters inserted developed CRT [IR 17.7 (13.5–23.2) CRTs/1000*cd], after 5 [3–10] days from insertion. Forty-six CRTs (88%) were partial thrombosis. All CRTs remained asymptomatic. Obesity and ECMO support were patient-related protective factors [IRR 0.24 (0.10–0.60), p = 0.002 and 0.05 (0.01–0.50), p = 0.011, respectively]. The internal jugular vein had higher CRT IR than other sites [20.1 vs. 5.9 CRTs/1000*cd, IRR 4.22 (1.22–14.63), p = 0.023]. Pulmonary artery catheter and left-side cannulation were catheter-related risk factors [IRR 4.24 (2.00–9.00), p < 0.001 vs. central venous catheters; IRR 2.69 (1.45–4.98), p = 0.002 vs. right cannulation, respectively]. No statistically significant effect of the number of simultaneously inserted catheters [IRR 1.11 (0.64–1.94), p = 0.708] and of the catheterization length [IRR 1.09 (0.97–1.22), p = 0.155] was detected. The ICU length of stay was longer in CRT patients (20 [15–31] vs. 6 [4–14] days, p < 0.001), while no difference in mortality was observed. Conclusions CRTs are frequent but rarely symptomatic. This study suggests that obesity and ECMO are protective factors, while pulmonary artery catheter, internal jugular vein and left-side positioning are risk factors for CRT.