Despite the publication of several randomized controlled trials (RCTs), it is not clear which technique for the treatment of focal chondral and osteochondral defects of the knee grants the best clinical outcome. The aim of this network meta-analysis (NMA) was to compare the efficacy and safety of microfractures (MF), autologous chondrocyte implantation (ACI), autologous matrix-induced chondrogenesis (AMIC), osteochondral autograft transplantation (OCT) at short (< 1 year), intermediate (1-5 years) and long-term (> 5 years). We carried out an NMA with Bayesian random-effect model, according to PRISMA guidelines. The search was performed in MEDLINE, EMBASE, Web of Science, CENTRAL, CINAHL, SPORTDiscus, clinicaltrials.gov, WHO ICTRP, from inception to November 2022. The eligibilities were randomized controlled trials on patients with knee chondral and osteochondral defects, undergoing microfractures, OCT, AMIC, ACI, without restrictions for prior or concomitant surgery on ligaments, menisci or limb alignment, prior surgery for fixation or ablation of osteochondritis dissecans fragments, and prior cartilage procedures as microfractures, drilling, abrasion, or debridement. Nineteen RCTs were included. No difference among treatments was shown in the pooled comparison of patient reported outcome measures (PROMs) at any timepoint. Safety data were not available for all trials due to the heterogeneity of reporting, but chondrospheres seemed to have lower failure and reoperation rates. This NMA showed no difference for PROMs with any technique. The lower failure and reoperation rates with chondrospheres must be interpreted with caution since adverse event data was heterogenous among trials. The standardization of the efficacy and safety outcome measures for future trials on knee cartilage repair and regeneration is necessary.