Background: There has been little information on treatment patterns and factors affecting outcomes of metastatic or recurrent esophageal cancer (EC) in clinical practice before the marketing of immune checkpoint inhibitors. This study aimed to investigate the treatment patterns and outcomes among patients (pts) with EC treated with systemic chemotherapy (CTx). Methods: This was a retrospective chart review study and included pts with histologically diagnosed esophageal squamous or adenosquamous carcinoma who started systemic CTx for metastatic or recurrent disease between January 1, 2013 and December 31, 2018 at 16 institutions in Japan. With a cutoff date of December 31, 2020, the treatment patterns and outcomes, including response rate (RR), progression-free survival (PFS), and overall survival (OS) for first through third CTx, were analyzed. Results: A total of 891 pts were included in this analysis. The median age (range) was 67 (23-90) years, 84.9% of pts were male, histological types were squamous cell carcinoma in 99.0% and adenosquamous carcinoma in 1.0%, and disease status was metastatic in 35.8% of pts. Most common first-, second-, and third-line regimens were fluoropyrimidine-based (72.4%), taxane-based (64.6%), and taxane-based (48.2%), respectively. Of the pts who received the first-line CTx, the second- and third-line CTx were administered in 51.2% and 21.4% of pts, respectively. The RR from first- to third-line CTx was 24.2%, 6.5%, and 2.2%, and mPFS was 4.1 months (mo) (95% CI 3.7-4.5), 3.1 mo (95% CI 2.8-3.6), and 3.0 mo (95% CI 2.5-4.2), respectively. The mOS from the first-, second-, and third-line CTx were 12.6 mo (95%CI 11.4-13.6), 8.3 mo (95% CI 7.7-9.6), and 8.0 mo (95% CI 7.1-9.5), respectively. As for OS from first-line CTx, a trend of improvement was shown before (median 11.9 mo, 95% CI 10.6-13.3) or after (median 13.2 mo, 95% CI 11.3-14.5) the median time of treatment initiation (March 2016). Pts with recurrent disease (mOS 26.6 mo, 95% CI 24.7-28.6) had a better prognosis than those with stage 4 disease at initial diagnosis (mOS 14.9 mo, 95% CI 13.2-16.3). Of the 293 pts who relapsed after esophagectomy with perioperative CTx or radical chemoradiotherapy, the time from the last day of CTx administration to relapse was less than 6 mo (early recurrence) in 123 (42.0%) pts and more than 6 mo (late recurrence) in 170 (58.0%) pts. The prognosis for pts with early recurrence (mOS 16.3 mo, 95% CI 13.7-20.2) was worse than for pts with late recurrence (mOS 32.9 mo, 95% CI 28.9-35.5). Conclusions: The results of this study revealed the actual treatment and prognosis of metastatic or recurrent EC in clinical practice. This real-world data might identify unmet needs and provide important information for the development of treatments in future.