Objectives To evaluate the efficacy of a slow release doxycycline gel (SRD) adjunctively administered to non‐surgical therapy in subjects with recurrent or persistent periodontitis but acceptable oral hygiene during supportive periodontal care. Material & methods In this single blind, parallel group, multicentre study, 202 of 203 recruited periodontal maintenance subjects with recurrent or persistent periodontitis were randomly assigned to subgingival ultrasonic/sonic instrumentation (USI) with (test) or without (control) subsequent administration of SRD in all residual periodontal pockets ≥4 mm. Intergroup differences in probing depth, BOP reductions, treatment time, probing attachment levels were evaluated at 3, 6 and 12 months. The primary outcome was the inter‐group difference in absolute change of probing pocket depth (PPD) 3, 6 and 12 months after intervention. Results At baseline, the two groups were comparable. At 3 months, the test group showed a significantly higher decrease in mean probing depth than the control group at 3 months (mean difference = 0.11 mm, 95% CI 0.03–0.19 mm, p = 0.003). Administration of SRD resulted in significantly greater odds of transition of bleeding pockets ≥5 mm to a category of non bleeding sites with PPD ≤4 mm at 3 and 6 months (O.R. = 1.4, 95% CI 1.2–1.8 at 3 months). At 6 months, SRD benefit was observed only in the deeper pockets. 7.5% of subjects (no significant difference between test and control) showed disease progression (attachment loss ≥2 mm) and were exited from the study. No difference in the incidence of adverse events was observed between groups. Conclusion The trial results show that topically administered SRD may provide short‐term benefit in controlling inflammation and deep pockets in treated periodontal patients participating in a secondary prevention programme and able to maintain a satisfactory level of oral hygiene.