Introduction and hypothesis Loss of anatomical support for the pelvic organs results in pelvic organ prolapse (POP). We hypothesized that daily self-management of a cube pessary might be a safe, feasible long-term treatment in women with symptomatic POP. Methods A cohort of 214 symptomatic POP patients (stage 2+) were enrolled prospectively (January to December 2015). Each patient was size-fitted with a space-filling cube pessary and completed a questionnaire online or by phone ≥5 years after her initial fitting. Change in quality of life (QoL) was measured with the Patient Global Impression of Improvement (PGI-I). Results Of 185 women included in our analyses, 174 (94%) were continuing to use their pessary 4 weeks post-insertion. Among those, 143 (82.2%) used the pessary successfully for ≥5 years. A large majority of these patients (88.8% [127 out of 143]) described their condition as much or very much improved compared with their pretreatment status (PGI–I). Adverse secondary effects (ASEs) were infrequent [15.4% (22 out of 143)]; when they did occur, they were mild, including smelly vaginal discharge (15 out of 22) and slight vaginal bleeding caused by the fitting procedure (6 out of 22). Conclusions Daily self-management of cube pessaries was found to be a safe and effective treatment for improving POP-related symptoms and QoL in the long term.