Introduction Carfilzomib plus dexamethasone (Kd) is widely used in patients with relapsed and/or refractory multiple myeloma (RRMM). However, the treatment outcomes of Kd, especially in trial-unfit patients, have not been extensively studied in the real-world setting. Methods We analyzed the outcomes of 152 RRMM patients who received Kd at our hospitals from April 2018 to March 2022. Results At the commencement of Kd, they received a median of two (range, 1–7) lines of prior anti-myeloma therapy. According to the ENDEAVOR study criteria, 93 (61.2%) and 59 (38.8%) patients were classified as the trial-fit and the trial-unfit group, respectively. The overall response (OR) rate for the entire cohort was 71.1% (95% CI: 63.2%-78.1%). Median time-to-next treatment (TTNT) and overall survival (OS) were 8.0 months (95% CI: 6.8–10.8 months) and 22.8 months (95% CI: 13.4–38.0 months), respectively. There was no significant difference in the OR rate between the trial-fit and the trial-unfit groups (76.3% vs. 62.7%; P = 0.105). However, the median TTNT (5.8 vs. 10.3 months; P < 0.001) and OS (15.0 vs. 36.8 months; P = 0.009) were significantly shorter in the trial-unfit group. On multivariate analysis, trial-fitness (unfit vs. fit) remained a significant covariate affecting the TTNT (HR: 1.65, 95% CI: 1.14–2.40; P < 0.001). Conclusion Our data suggest that the treatment outcomes of Kd are acceptable in the real-world setting, with significant differences between the trial-fit and the trial-unfit groups, although they are relatively inferior to those of a pivotal trial.