We conducted a randomized, controlled trial to evaluate different strategies of offering an HPV‐self sampling program, and compared this with two control groups. All total of 35,354 women who did not participate in the Flemish cancer screening program were included in the study: 9,118 received a HPV self‐collection brush (RIATOL qPCR HPV genotyping test (qPCR [E6/E7]); 9,098 were offered the opportunity to order an HPV‐selfsampling brush, 8,830 received the recall letter; 8,849 received no intervention. Within 12 months after the mailing, 18.7% of the women who had received the brush, participated by returning a self‐sample sample, while 10.6% women allocated to the opt‐ in group did so. 10.5% women who received the standard recall letter, had a PAP smear taken within a period of 12 months; while 8% women did so without receiving an intervention at all. Participation in postmenopausal women was higher than in women younger than 50 in both self‐sampling arms. Screening by means of the self‐sample kit increased by age, contradictory when screening is performed by a PAP smear. Of those testing hrHPV positive (9.5%), 88.9% attended for follow up cytology. The mean DNA concentration, found in the self‐sampler, decreased by age, causing a higher number of inconclusive results. Our results support the efficacy of a self‐sampling strategy to increase participation in the Flemish screening program. Self‐sampling seems particularly acceptable to postmenopausal non‐responders. Future research should focus on the performance of different self‐sampling devices in post‐menopausal women as low DNA concentrations exponentially increased over age.