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Abstract Background This study aimed to evaluate spatial changes in dental arches resulting from premature loss of first primary molars and assess the necessity of a space maintainer. Methods We searched the electronic databases PubMed, Cochrane Library, ClinicalTrials, and EMBASE. Split-mouth studies involving unilateral premature loss of a primary first molar were included. Quality assessment of selected studies made use of the ROBINS-I tool. Mean space differences were calculated for the D + E and D spaces, arch width, arch length, arch perimeter. Results Of the 329 studies considered, 11 split-mouth studies were selected, including 246 cases in the maxilla and 217 in the mandible from 477 individuals aged 5–10 years. Over the medium-term follow-up period (6–24 months), space loss was 0.65 mm in the maxillary D + E (MD 0.65, 95% CI 0.15–1.16, P = 0.01), 1.24 mm in the mandibular D + E (MD 1.24, 95% CI 0.60–1.89, P < 0.01), and 1.47 mm in the mandibular D (MD 1.47, 95% CI 0.66–2.28, P < 0.01). There was no significant change in arch width, length, or arch perimeter between the initial and follow-up examinations (P > 0.05). Conclusions After premature loss of first primary molars, space can be lost, but the amount of loss would not affect arch width, length, or arch perimeter over the 6–24 months follow-up period.