To evaluate the rate of disease progression and the factors associated with such progression in patients with an ultrasound diagnosis of adenomyosis. This was a single center, prospective, observational, cohort study performed at a tertiary referral center. Patients who obtained an ultrasound diagnosis of adenomyosis from May 2022 to August 2022 were recruited. Demographic, clinical and ultrasound data were recorded at the first visit (T0) and after 12 months (T1) for enrolled patients and compared between T0 and T1. The study population was divided in two groups according to progression (increase in uterine volume >20%) or stability/regression (decrease or increase in uterine volume ≤20%) of adenomyosis at T1. Primary study outcome was the rate of adenomyosis progression, while secondary study outcome was the association of adenomyosis progression with demographic and clinical factors. Post hoc subgroups analyses for primary and secondary study outcomes were performed based on hormonal therapy (untreated and treated). A total of 221 patients were enrolled in the study, with no significant difference in terms of baseline data among the two study groups and no patients were lost to follow-up. The overall rate of adenomyosis progression was 21.3% (47/221 patients). The rate was 30.77% in hormonally untreated women, and 18.34% in hormonally treated women. Progression was associated with the presence of focal adenomyosis of the outer myometrium (P = 0.037), moderate to severe dysmenorrhea (P = 0.001), chronic pelvic pain (P = 0.05), dyschezia (P = 0.05), and worsening of chronic pelvic pain (P = 0.04) at T1. Adenomyosis showed a rate of disease progression of 21.3% at the 12-month follow-up (30.77% in hormonally untreated women, and 18.34% in hormonally treated women). The presence and/or worsening of painful symptoms, such as severe dysmenorrhea, dyschezia and chronic pelvic pain, as well as the presence focal adenomyosis of the outer myometrium, might help identify patients at higher risk of disease progression and tailor their follow-up.