Aim: Insight in health-related quality of life (HRQoL) may improve clinical decision making and inform patients about the long-term effects of gastrectomy. This study aimed to evaluate and identify factors associated with HRQoL after gastrectomy. Methods: This cross-sectional study used prospective databases from seven Dutch centers (2001–2015) including patients who underwent gastrectomy for cancer. Between July 2015 and November 2016, European Organization for Research and Treatment of Cancer HRQoL questionnaires QLQ-C30 and QLQ-STO22 were sent to all surviving patients without recurrence. The QLQ-C30 scores were compared to a Dutch reference population using a one-sample t test. Spearman’s rank test was used to correlate time after surgery to HRQoL, and multivariable linear regression was performed to identify factors associated with HRQoL. Results: A total of 222 of 274 (81.0%) patients completed the questionnaires. Median follow-up was 29 months (range, 3–171) and 86.9% of patients had a follow-up >1 year. The majority of patients had undergone neoadjuvant treatment (64.4%) and total gastrectomy (52.7%). Minimally invasive gastrectomy (MIG) was performed in 50% of the patients. Compared to the general population, gastrectomy patients scored significantly worse on most functional and symptom scales (p < 0.001) and slightly worse on global HRQoL (78 vs. 74, p = 0.012). Time elapsed since surgery did not correlate with global HRQoL (Spearman’s ρ = 0.06, p = 0.384). Distal gastrectomy, neoadjuvant treatment, and MIG were associated with better HRQoL (p < 0.050). Conclusion: After gastrectomy, patients encounter functional impairments and symptoms, but experience only a slightly impaired global HRQoL. Distal gastrectomy, the ability to receive neoadjuvant treatment, and MIG may be associated with HRQoL benefits.