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Background Most people around the world do not have access to facility-based diagnostic testing, and the gap in availability of diagnostic tests is a major public health challenge. Self-testing, self-sampling, and institutional testing outside conventional clinical settings are transforming infectious disease diagnostic testing in a wide range of low- and middle-income countries (LMICs). We examined the delivery models of infectious disease diagnostic testing outside clinics to assess the impact on test uptake and linkage to care. Methods We conducted a systematic review and meta-analysis, searching 6 databases and including original research manuscripts comparing testing outside clinics with conventional testing. The main outcomes were test uptake and linkage to care, delivery models, and adverse outcomes. Data from studies with similar interventions and outcomes within thematic areas of interest were pooled, and the quality of evidence was assessed using GRADE. This study was registered in PROSPERO (CRD42019140828). We identified 10 386 de-duplicated citations, and 76 studies were included. Data from 18 studies were pooled in meta-analyses. Studies focused on HIV (48 studies), chlamydia (8 studies), and multiple diseases (20 studies). HIV self-testing increased test uptake compared with facility-based testing (9 studies: pooled odds ratio [OR], 2.59; 95% CI, 1.06–6.29; moderate quality). Self-sampling for sexually transmitted infections increased test uptake compared with facility-based testing (7 studies: pooled OR, 1.74; 95% CI, 0.97–3.12; moderate quality). Conclusions.  Testing outside of clinics increased test uptake without significant adverse outcomes. These testing approaches provide an opportunity to expand access and empower patients. Further implementation research, scale-up of effective service delivery models, and policies in LMIC settings are needed. [ABSTRACT FROM AUTHOR]