BACKGROUND: Obstructive sleep apnea (OSA) is commonly treated with continuous positive airway pressure (CPAP), though many patients struggle with adherence. Sleep positional therapy (SPT) offers a potential alternative, especially for positional OSA (POSA). This study aimed to compare the efficacy and safety of SPT with CPAP, oral appliance therapy (OAT), and placebo. METHODS: Nineteen randomized controlled trials (RCTs) with 1,231 participants were included. Data extraction focused on changes in key outcomes such as apnea-hypopnea index (AHI), total sleep time (TST), oxygen desaturation index (ODI), and sleep architecture from pre- to post-intervention. Random-effects meta-analyses were conducted to compare mean changes between SPT and control groups (placebo, OAT, CPAP), with sensitivity analyses to assess heterogeneity. RESULTS: Sleep positional therapy (SPT) showed a significant reduction in AHI in the supine position compared to placebo (MD = -7.46, 95% CI: -11.42, -3.49), although no difference was observed in overall AHI between SPT and placebo or OAT. Compared to CPAP, SPT was less effective in reducing AHI, with a trend toward greater reductions in AHI favoring CPAP. SPT demonstrated a significant improvement in arousal index compared to OAT (MD = -7.11, 95% CI: -10.52, -3.71) and a lower risk of device-related complications compared to both OAT (OR = 0.54, 95% CI: 0.31, 0.95) and CPAP (OR = 0.29, 95% CI: 0.12, 0.72). However, SPT did not lead to significant improvements in TST or oxygen saturation parameters across comparisons. CONCLUSION: Sleep positional therapy (SPT) is a safe alternative for managing positional OSA, particularly for patients intolerant to CPAP, though it remains less effective than CPAP in reducing overall AHI and improving oxygenation.