Objectives <p>This examiner-blinded, randomized controlled trial compared the plaque removal efficacy of a triple-headed manual toothbrush (3HB) to a conventional manual toothbrush.</p> Materials and methods <p>Forty-eight non-smoker, right-handed participants (aged 20–50 years) were randomly grouped: The first group (Conventional Manual Toothbrush-CMB) was given a manual toothbrush and the second group (3Head Brush-3HB) was given a toothbrush with a 3-head geometric design. All participants were assessed with The Rustogi et al. Modified Navy Plaque Index (RMNPI). Clinical trial registration number of the present study is “NCT06594757”.</p> Results <p>Forty-eight eligible participants were randomized into two groups (<i>n</i> = 24 each). No significant differences in baseline demographics were observed. Plaque scores evaluated before and after brushing showed no significant difference between the groups in marginal, aproximal, anterior, premolar and whole mouth regions. However, there was a statistically significant decrease in plaque scores in all regions after brushing in both groups (<i>p</i> &lt; 0.001). There was also no significant difference between genders in terms of plaque scores, while plaque reduction was effective regardless of age or gender in all regions after brushing (<i>p</i> &lt; 0.001). The findings suggest that both toothbrush designs are effective in plaque removal.</p> Conclusions <p>The triple-headed manual toothbrush demonstrated plaque removal efficacy statistically comparable to, but not superior to, the conventional manual toothbrush in healthy, non-impaired adults. Its clinical advantage may be specific to populations with manual dexterity challenges.</p> Clinical relevance <p>Problems related to teeth and gums can be prevented and controlled by appropriate mechanical cleaning of dental plaque. In order to successfully remove microbial dental plaque, teeth should be brushed regularly, for sufficient time and with the correct technique. Toothbrush manufacturers continue to work to remove plaque better with different designs of the head of the toothbrush. It is tried to increase the plaque removal efficiency of classical brushes with different designs of areas such as bristles, handle, head angle and structure. The effectiveness of different toothbrush designs has been demonstrated in studies investigating plaque removal efficiency, especially in interproximal and gingival areas that can be cleaned more difficult. This study’s results demonstrated that removing plaque from the tooth surface by effective tooth brushing may help improve oral health.</p> Trial registration <p>ClinicalTrials.gov Identifier: NCT06594757, registered on September 09, 2024 (retrospectively registered).</p>