Background: Computer-assisted screening of cervical liquid-based cytology (LBC) preparations using the ThinPrep® Imaging System (TIS) has shown improved qualitative and quantitative gains. The use of Multicyte™ has not been described in a well-established national screening programme with a low incidence of high-grade dyskaryosis. Objectives: To assess the impact of computer-assisted screening within the Scottish Cervical Screening Programme (SCSP). Methods: Two groups of three laboratories, each sharing a ThinPrep® Imager, screened 79366 slides randomized to test and 90551 to control arms by laboratory accession. Screeners were not blinded. Standard laboratory reporting profiles of the SCSP, sensitivity, specificity and false-negative rates of all grades of LBC abnormalities with respect to final cytology reports, predictive value for cervical intraepithelial neoplasia grade 2 or worse (CIN2+) on histology; and screening rates were compared for both arms. Results: Inadequate and negative reporting rates were significantly lower and low-grade reporting rates significantly higher in the imager arm. Imager-assisted screening showed significantly better specificity than manual screening with respect to the final cytology result. There was no evidence of a significant difference in the detection of CIN2+ or CIN3+. Positive, abnormal and total predictive values (high-grade, low-grade and all abnormal cytology found to be CIN2+, respectively) were similar in both arms. Productivity was significantly higher in the imager arm. Conclusion: Computer-assisted screening in a well established screening programme showed significantly improved productivity without loss of quality. These findings should inform future policy for cervical screening programmes.