The primary aim of this systematic review was to assess the evidence on periodontal disease progression after treatment in patients receiving supportive periodontal therapy (SPT) and to identify predictors of clinical attachment level (CAL) loss. A protocol was developed to answer the following focused question: In adult patients treated for periodontitis, what is the disease progression in terms of CAL loss after surgical or non-surgical treatment? Randomized controlled clinical trials, prospective cohort studies, and longitudinal observational human studies with a minimum of 5 years of follow-up after surgical or non-surgical treatment that reported CAL and probing depth changes were selected. Seventeen publications reporting data from 14 investigations were included. Data from 964 patients with a follow-up range of 5–15 years was evaluated. When the CAL at the latest follow-up was compared to the CAL after active periodontal therapy, 10 of the included studies reported an overall mean CAL loss of ≤0.5 mm, 3 studies reported a mean CAL loss of 0.5–1 mm, and 4 studies reported a mean CAL loss of >1 mm. Based on 7 publications, the percentage of sites showing a CAL loss of ≥2 mm varied from 3% to 20%, and a high percentage of sites with CAL loss was associated with poor oral hygiene, smoking, and poor compliance with SPT. The outcomes after periodontal therapy remained stable over time. Disease progression occurred in a reduced number of sites and patients, mostly associated with poor oral hygiene, poor compliance with SPT, and smoking.