Background/Rationale Weekly cholecalciferol can be an alternative to daily supplementation to reduce pill burden in patients with complex medication regimens and hypovitaminosis D, but evidence supporting this switch is unclear. Objective We aimed to determine whether weekly cholecalciferol was superior to daily cholecalciferol to replete patients with hypovitaminosis D. Methods We conducted a systematic review of randomized controlled trials involving participants with baseline hypovitaminosis D (<30ng/ml) comparing weekly versus daily cholecalciferol dosing and where serum cholecalciferol was measured within 90 days of starting treatment. We searched MEDLINE, CINAHL and EMBASE from inception to May 7 ^th, 2024. A random-effects meta-analysis evaluated the odds ratio for repletion of serum Vitamin D levels. Findings Eight trials involving 542 patients were included in the analysis. Weekly D3 and daily cholecalciferol were not significantly different in correcting hypovitaminosis D (OR=1.5, 95% CI = 0.3-6.9, p=0.6, favoring weekly dosing, I ²=85.3%). A sensitivity analysis excluding otherwise healthy patients had similar findings (OR=0.8, 95% CI=0.3–2.1, p=0.6). Most studies were judged to be at risk of bias, the different doses being compared increased the heterogeneity (I ²=85.3%). Conclusions There is limited direct evidence supporting a switch from daily to weekly cholecalciferol dosing; however, weekly supplementation was not demonstrably worse at repleting levels and decreases a patient’s daily pill burden.