Background: We compared the effect of general anesthetics on postoperative quality of recovery between propofol-based total intravenous anesthesia (TIVA) and inhalation anesthesia. Methods: In this randomized, single-blinded trial, 150 patients undergoing robot-assisted or laparoscopic nephrectomy for renal cancer were randomly allocated to either the TIVA or desflurane anesthesia (DES) group. Postoperative recovery was evaluated using the Korean version of the Quality of Recovery-15 questionnaire (QoR-15K) at 24 h, 48 h, and 72 h postoperatively. A generalized estimating equation (GEE) was performed to analyze longitudinal QoR-15K data. Opioid consumption, pain severity, the occurrence of postoperative nausea and vomiting, and quality of life at three weeks after discharge were also compared.Results: Data were analyzed for 70 patients in each group. The TIVA group showed a significantly higher QoR-15K score at 24 and 48 h postoperatively (24 h: DES, 96 [IQR: 77–109] vs. TIVA, 104 [IQR: 82–117], median difference 8 [95% CI: 1–15], p = 0.029; 48 h: DES, 110 [IQR: 95–128] vs. TIVA, 125 [IQR: 109–130], median difference 8 [95% CI: 1–15], p = 0.022), however not at 72 h (p = 0.400). During the entire study period, the GEE revealed significant effects of group (adjusted mean difference 6.2, 95% CI: 0.39–12.1, p = 0.037) and time (p < 0.001) on postoperative QoR-15K scores, without group-time interaction (p = 0.051). However, there were no significant differences at other time points and in other postoperative outcomes, except opioid consumption, during the first 24 h postoperatively.Conclusions: Propofol-based TIVA showed only a transient and marginal improvement in postoperative recovery compared to desflurane anesthesia, which would have been difficult to lead to significant differences in other postoperative outcomes.Trial registration: Clinicaltrials.gov, NCT04447105 (date of registration: June 25, 2020)