Research results suggest the potential of topical adenosine as a hair-promoting agent. The aim of this study was to examine the available clinical evidence of the efficacy of topical adenosine products in hair loss. This systematic review was conducted in accordance with PRISMA and PICO guidelines and included articles indexed in PubMed, Scopus, and Web of Science. The strength of evidence was assessed according to the GRADE system. Wherever feasible, data were extracted for a meta-analysis. Among 8625 articles returned by the query, 7 clinical trials were identified of topical adenosine (lotion, shampoo) in hair loss. They unanimously reported on a reduction in hair loss and increase in hair density (strength of evidence very low to moderate). A meta-analysis of three eligible trials showed a tendency to increased hair density (OR = 1.03, 95% CI: 0.89–1.20, p = 0.68), an increase in thick hair (OR = 1.4, 95% CI: 0.82–2.38, p = 0.21) and a decrease in thin hairs (OR = 0.93, 95% CI: 0.61–1.43, p = 0.75) after 6 months of alopecia treatment with a 0.75% adenosine lotion. The results from clinical trials published until now suggest that topical adenosine increases hair thickness, reduces excessive hair loss, stimulates hair regrowth, and increases hair density. The overall strength of evidence remains low due to flawed design and small sample sizes in most trials. Nevertheless, topical adenosine products seem worth trying, especially in the case of contraindications or adverse effects to approved medicinal products for hair loss. Further, better designed trials of adenosine in hair loss are warranted.