Purpose: Spectacle non-tolerance or adverse events to spectacle wear are serious concerns for both patients and practitioners. Non-tolerance may contribute to a negative impact on the practitioner’s ability and practice. Therefore, a detailed understanding of frequency and causes of spectacle non-tolerance in clinical ophthalmic practice is essential. This review aimed to determine the prevalence and causes of non-tolerance to spectacles prescribed and dispensed in clinical practice. Method: The current systematic review included quantitative studies published in the English language that reported spectacle non-tolerance in clinical practice. A comprehensive search was conducted in PubMed, Scopus and the Web of Science database for studies published until 13 July 2020. An adapted version of the Newcastle-Ottawa Scale (NOS) modified for cross-sectional studies was used to assess the quality of each included study. Five investigations with 205,478 study participants were included in the review. The prevalence of spectacle non-tolerance from individual studies was pooled using MetaXL software. The pooled prevalence of spectacle non-tolerance was 2.1% (95% CI: 1.6–2.7) ranging from 1.6% to 3.0%. The papers were also reviewed to identify the potential causes of non-tolerances. Nearly half reported that non-tolerance (47.4%) was due to an error in refraction. Other causes identified were errors related to communication (16.3%), dispensing (13.5%), non-adaptation (9.7%), data entry (8.7%), binocular vision (7.4%) and ocular pathology (6.4%). Summary: This review improves our understanding of spectacle non-tolerance in clinical practice. This is important because non-tolerance may lead to spectacle wear discontinuation, which may deprive patients of optimal vision. Increased non-tolerance in clinical practice may affect a clinician’s reputation and incur additional costs associated with reassessments and replacements. Spectacle non-tolerance occurred due to a multitude of factors related to optical dispensing and wearer adaptation. Therefore, there is a need for vigilance while prescribing spectacles. The limited evidence highlights the need for more studies, especially in limited-resource settings, to improve the quality of refractive error services.