Background and objective Since 1997 several meta-analyses (MA) of placebo-controlled randomised efficacy trials of homoeopathy for any indication (PRETHAI) have been published, with different methods, results, and conclusions. To date, a formal assessment of these MA has not been undertaken. Main research objective for this systematic review was efficacy of homoeopathic treatment in MA of PRETHAI. Methods Inclusion criteria: MA of PRETHAI in humans; all ages, countries, settings, publication languages; published 1.1.1990-31.10.2020. Exclusion criteria: systematic reviews without MA; MA restricted to age or gender groups, specific indications, or specific homoeopathic treatments; MA not including efficacy. We searched 8 online databases (completed 14.12.2020). Primary outcome was the effect estimate for all included trials in each MA and after sample restriction to trials of higher methodological quality, according to predefined criteria. Risk of bias of MA was assessed by ROBIS. Quality of evidence was assessed by GRADE. Data synthesis was the proportion of MA showing a significant positive effect of homoeopathy vs. no significant difference. Results Six MA were included, covering individualised homoeopathy (I-HOM, n = 2), non-individualised homoeopathy (NI-HOM, n = 1) and all homoeopathy types (ALL-HOM = I-HOM + NI-HOM, n = 3), respectively. The MA comprised between 16 and 110 trials, published 1943-2014, with a median trial sample size of 45 to 97 patients. Risk of bias (low/unclear/high) was rated as low for three MA and high for three. Effect estimates for all trials in each MA showed a significant positive effect of homoeopathy, compared to placebo (5 of 5 MA, no data in 1 MA). Sample restriction to high-quality trials was available from 4 trials, the effect remained significant in 3 MA (thereof 2x ALL-HOM, 1x I-HOM) and was no longer significant in 1 MA of NI-HOM. Discussion The quality of evidence for positive effects of homoeopathy beyond placebo (high / moderate / low / very low) was high for I-HOM and moderate for ALL-HOM as well as for NI-HOM. There was no support for the alternative hypothesis of no outcome difference between homoeopathy and placebo. The available MA of PRETHAI show significant positive effects of homoeopathy beyond placebo. This is in accordance with laboratory experiments showing effects, in part reproducible, of homoeopathically potentised preparations in physico-chemical, in-vitro, plant-based and animal-based test systems. Other Primary funding sources: Christophorus-Stiftung, Stuttgart, DE; Stiftung Marion Meyenburg, Hamburg, DE; Dr. Hauschka-Stiftung, Bad Boll/Eckwälden, DE. Registration: PROSPERO, CRD42020209661