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The aim of this study was to compare the uptake of mail-delivered tests for colorectal cancer screening. We assessed the effect of an advance notification letter and a reminder letter, and analysed the proportion of inappropriately handled tests.Fifteen thousand randomly selected residents of Latvia aged 50–74 years were allocated to receive one of three different test systems: either a guaiac faecal occult blood test (gFOBT) or one of two laboratory-based immunochemical tests (FIT) – FOB Gold or OC-Sensor. Half of the target population received an advance notification letter; all nonresponders were sent a reminder letter.The uptake of screening was 31.2% for the gFOBT, 44.7% for FOB Gold and 47.4% for the OC-Sensor (odds ratio 0.55; 95% confidence interval 0.51–0.60 for gFOBT vs. FOB Gold; odds ratio 0.90; 95% confidence interval 0.83–0.98 for FOB Gold vs. OC-Sensor). The uptake in the gFOBT group was improved by the advance notification letter (7.7%, P<0.0001). 30.9% returned tests were received after the reminder letter. The proportion of tests that could not be analysed because of inadequate handling was 0.9% for gFOBT, 4.4% for FOB Gold and 0.2% for the OC-Sensor (P=0.002 for gFOBT vs. OC-Sensor; P<0.001 for all comparisons vs. FOB Gold).The use of FIT resulted in higher uptake. Receipt of a reminder letter was critical to participation, but the use of an advance notification letter was important mainly for gFOBT. The proportion of inappropriately handled tests was markedly higher for FOB Gold.