Abstract Introduction Our group has previously reported our experience with autologous skin cell suspension (ASCS) in the treatment of all subjects with hand burns regardless of the total body surface area (TBSA) involved. In order to better address the confounder of TBSA on burn outcomes, we sought to analyze our experience in a cohort of subjects whose TBSA totaled 20% or less. We hypothesized that the use of ASCS in conjunction with a 2:1 meshed autograft would provide comparable outcomes to hand burns treated with smaller meshed autograft alone. Methods A retrospective review was conducted for deep 2nd and 3rd degree hand burns treated with split thickness autograft (STAG) at our urban verified burn center between April 2018 to September 2020. Exclusion criterion was a TBSA greater than 20%. The cohorts were those subjects treated with ASCS in combination with STAG (ASCS(+)) versus those treated with STAG alone (ASCS(-)). All ASCS(+) subjects were treated with 2:1 meshed STAG and ASCS overspray while all ASCS(-) subjects had 1:1 or piecrust mesh only. Outcomes included demographics, proportion returning to work (RTW), length of time for RTW, and time to wound closure. Mann-Whitney U test was used for comparisons of continuous variables, and Fishers Exact test for categorical variables. Values are reported as median and interquartile range. Results Fifty-one subjects fit the study criteria (ASCS(+) n=31, ASCS(-) n=20). The ASCS(+) group was significantly older than the ASCS(-) cohort (44 yrs. [32, 54] vs 32 [27.5, 37], p=0.009) with larger %TBSA burns (15% [9.5, 17] vs 2% [1, 4], p < 0.0001), and larger size hand burns (190 cm2 [120, 349.5] vs 126 cm2 [73.5, 182], p=0.015). Comparable results were seen between ASCS(+) and ASCS(-), respectively, for time to wound closure (9 days [7, 13] vs 11.5 [6.75, 14], p=0.63), proportion RTW (61% vs 70%, p=0.56), and days for RTW among those returning (35 [28.5, 57] vs 33 [20.25, 59], p=0.52). The ASCS(+) group had two graft infections with no reoperations, while ASCS(-) had one infection with one reoperation. No subjects in either group had a dermal substitute placed. Conclusions Despite being significantly older, having larger hand wounds, and larger overall wounds within the parameters of the study criteria, patients with 20% TBSA burns or smaller whose hand burns were treated with 2:1 mesh and ASCS overspray had comparable time to wound closure and return to work as subjects treated with 1:1 or pie-crust meshed STAG. Our group plans to follow this work with scar assessments for a more granular picture of pliability and reconstructive needs.