BACKGROUND AND PURPOSE: We aimed to compare single incision laparoscopic cholecystectomy (SILC) to the standard multiport technique (MLC) for clinically relevant outcomes in adults. ----- METHODS: Systematic review and random-effects meta-analysis of randomized trials. ----- RESULTS: We identified 30 trials (SILC N = 1209, MLC N = 1202) mostly of moderate to low quality. Operating time (30 trials): longer with SILC (WMD = 12.4 min, 95% CI 9.3, 15.5; p < 0.001), but difference reduced with experience - in 10 large trials (1321 patients) WMD = 5.9 (-1.3, 13.1; p = 0.105). Intra-operative blood loss (12 trials, 1201 patients): greater with SILC, but difference practically irrelevant (WMD = 1.29 mL, 0.24-2.35; p = 0.017). Procedure failure (27 trials, 2277 patients): more common with SILC (OR = 13.9, 4.34-44.7; p < 0.001), but overall infrequent (SILC pooled incidence 4.39%) and almost exclusively addition of a trocar. Post-operative pain (29 trials) and hospital stay (22 trials): no difference. Complications (30 trials): infrequent (SILC pooled incidence 5.35%) with no overall SILC vs. MLC difference. Incisional hernia (19 trials, 1676 patients): very rare (15 vs. 4 cases), but odds significantly higher with SILC (OR = 4.94, 1.26-19.4; p = 0.025). Cosmetic satisfaction (16 trials, 11 with data at 1-3 months): in 5 trials with non-blinded patients (N = 513) in favour of SILC (SMD = 1.83, 0.13, 3.52; p = 0.037), but in 6 trials with blinded patients (N = 719) difference small and insignificant (SMD = 0.42, -1.12, 1.96; p = 0.548). ----- DISCUSSION: SILC outcomes largely depend on surgeon's skill, but regardless of it, when compared to MLC, SILC requires somewhat longer operating time, risk of incisional hernia is higher (but overall very low) and early cosmetic benefit is modest. ----- CONCLUSION: From the (in)convenience and safety standpoint, SILC is an acceptable alternative to MLC with a modest cosmetic benefit.